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1.
Cells ; 13(9)2024 Apr 28.
Article in English | MEDLINE | ID: mdl-38727293

ABSTRACT

BACKGROUND: Since cytokine receptor-like factor 1 (CRLF1) has been implicated in tissue regeneration, we hypothesized that CRLF1 released by mesenchymal stem cells can promote the repair of osteochondral defects. METHODS: The degree of a femoral osteochondral defect repair in rabbits after intra-articular injections of bone marrow-derived mesenchymal stem cells (BMSCs) that were transduced with empty adeno-associated virus (AAV) or AAV containing CRLF1 was determined by morphological, histological, and micro computer tomography (CT) analyses. The effects of CRLF1 on chondrogenic differentiation of BMSCs or catabolic events of interleukin-1beta-treated chondrocyte cell line TC28a2 were determined by alcian blue staining, gene expression levels of cartilage and catabolic marker genes using real-time PCR analysis, and immunoblot analysis of Smad2/3 and STAT3 signaling. RESULTS: Intra-articular injections of BMSCs overexpressing CRLF1 markedly improved repair of a rabbit femoral osteochondral defect. Overexpression of CRLF1 in BMSCs resulted in the release of a homodimeric CRLF1 complex that stimulated chondrogenic differentiation of BMSCs via enhancing Smad2/3 signaling, whereas the suppression of CRLF1 expression inhibited chondrogenic differentiation. In addition, CRLF1 inhibited catabolic events in TC28a2 cells cultured in an inflammatory environment, while a heterodimeric complex of CRLF1 and cardiotrophin-like Cytokine (CLC) stimulated catabolic events via STAT3 activation. CONCLUSION: A homodimeric CRLF1 complex released by BMSCs enhanced the repair of osteochondral defects via the inhibition of catabolic events in chondrocytes and the stimulation of chondrogenic differentiation of precursor cells.


Subject(s)
Cell Differentiation , Chondrocytes , Chondrogenesis , Mesenchymal Stem Cells , Animals , Rabbits , Mesenchymal Stem Cells/metabolism , Chondrogenesis/genetics , Chondrocytes/metabolism , Receptors, Cytokine/metabolism , Receptors, Cytokine/genetics , Femur/pathology , Signal Transduction , Cell Line , Mesenchymal Stem Cell Transplantation
2.
Sci Rep ; 14(1): 11390, 2024 05 18.
Article in English | MEDLINE | ID: mdl-38762569

ABSTRACT

This study performed three-dimensional (3D) magnetic resonance imaging (MRI)-based statistical shape analysis (SSA) by comparing patellofemoral instability (PFI) and normal femur models, and developed a machine learning (ML)-based prediction model. Twenty (19 patients) and 31 MRI scans (30 patients) of femurs with PFI and normal femurs, respectively, were used. Bone and cartilage segmentation of the distal femurs was performed and subsequently converted into 3D reconstructed models. The pointwise distance map showed anterior elevation of the trochlea, particularly at the central floor of the proximal trochlea, in the PFI models compared with the normal models. Principal component analysis examined shape variations in the PFI group, and several principal components exhibited shape variations in the trochlear floor and intercondylar width. Multivariate analysis showed that these shape components were significantly correlated with the PFI/non-PFI distinction after adjusting for age and sex. Our ML-based prediction model for PFI achieved a strong predictive performance with an accuracy of 0.909 ± 0.015, and an area under the curve of 0.939 ± 0.009 when using a support vector machine with a linear kernel. This study demonstrated that 3D MRI-based SSA can realistically visualize statistical results on surface models and may facilitate the understanding of complex shape features.


Subject(s)
Imaging, Three-Dimensional , Joint Instability , Machine Learning , Magnetic Resonance Imaging , Patellofemoral Joint , Humans , Magnetic Resonance Imaging/methods , Female , Male , Imaging, Three-Dimensional/methods , Joint Instability/diagnostic imaging , Patellofemoral Joint/diagnostic imaging , Patellofemoral Joint/pathology , Adult , Young Adult , Femur/diagnostic imaging , Femur/pathology , Adolescent
3.
ACS Appl Mater Interfaces ; 16(19): 25317-25332, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38706308

ABSTRACT

This investigation aimed to construct a bilayer scaffold integrating alginate and gelatin with nanobioactive glass (BG), recognized for their efficacy in tissue regeneration and drug delivery. Scaffolds, namely, alginate/gelatin (AG), alginate-/actonel gelatin (AGD), alginate actenol/gelatin-45S5 BG (4AGD), and alginate-actonel/gelatin-59S BG (5AGD), were assembled using a cost-effective freeze-drying method, followed by detailed structural investigation via powder X-ray diffraction as well as morphological characterization using field emission scanning electron microscopy (FESEM). FESEM revealed a honeycomb-like morphology with distinct pore sizes for nutrient, oxygen, and drug transport. The scaffolds evidently exhibited hemocompatibility, high porosity, good swelling capacity, and biodegradability. In vitro studies demonstrated sustained drug release, particularly for scaffolds containing actonel. In vivo tests showed that the bilayer scaffold promoted new bone formation, surpassing the control group in bone area increase. The interaction of the scaffold with collagen and released ions improved the osteoblastic function and bone volume fraction. The findings suggest that this bilayer scaffold could be beneficial for treating critical-sized bone defects, especially in the mandibular and femoral regions.


Subject(s)
Femur , Glass , Mandible , Tissue Scaffolds , Tissue Scaffolds/chemistry , Animals , Glass/chemistry , Mandible/diagnostic imaging , Mandible/surgery , Mandible/drug effects , Femur/drug effects , Femur/diagnostic imaging , Femur/pathology , Gelatin/chemistry , Bone Regeneration/drug effects , Alginates/chemistry , Porosity , Humans , Biocompatible Materials/chemistry , Biocompatible Materials/pharmacology , Tissue Engineering
4.
J Bone Miner Metab ; 42(3): 282-289, 2024 May.
Article in English | MEDLINE | ID: mdl-38704516

ABSTRACT

INTRODUCTION: Glucocorticoids delay fracture healing and induce osteoporosis. Angiogenesis plays an important role in bone repair after bone injury. Plasminogen activator inhibitor-1 (PAI-1) is the principal inhibitor of plasminogen activators and an adipocytokine that regulates metabolism. However, the mechanisms by which glucocorticoids delay bone repair remain unclear. MATERIALS AND METHODS: Therefore, we herein investigated the roles of PAI-1 and angiogenesis in glucocorticoid-induced delays in bone repair after femoral bone injury using PAI-1-deficient female mice intraperitoneally administered dexamethasone (Dex). RESULTS: PAI-1 deficiency significantly attenuated Dex-induced decreases in the number of CD31-positive vessels at damaged sites 4 days after femoral bone injury in mice. PAI-1 deficiency also significantly ameliorated Dex-induced decreases in the number of CD31- and endomucin-positive type H vessels and CD31-positive- and endomucin-negative vessels at damaged sites 4 days after femoral bone injury. Moreover, PAI-1 deficiency significantly mitigated Dex-induced decreases in the expression of vascular endothelial growth factor as well as hypoxia inducible factor-1α, transforming growth factor-ß1, and bone morphogenetic protein-2 at damaged sites 4 days after femoral bone injury. CONCLUSION: The present results demonstrate that Dex-reduced angiogenesis at damaged sites during the early bone-repair phase after femoral bone injury partly through PAI-1 in mice.


Subject(s)
Dexamethasone , Glucocorticoids , Neovascularization, Physiologic , Plasminogen Activator Inhibitor 1 , Animals , Mice , Plasminogen Activator Inhibitor 1/metabolism , Female , Glucocorticoids/pharmacology , Neovascularization, Physiologic/drug effects , Dexamethasone/pharmacology , Femur/drug effects , Femur/metabolism , Femur/pathology , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , Vascular Endothelial Growth Factor A/metabolism , Fracture Healing/drug effects , Mice, Knockout , Mice, Inbred C57BL , Bone Morphogenetic Protein 2/metabolism , Platelet Endothelial Cell Adhesion Molecule-1/metabolism , Angiogenesis
5.
Sci Rep ; 14(1): 12449, 2024 05 30.
Article in English | MEDLINE | ID: mdl-38816454

ABSTRACT

Bone graft granules implanted in bone defects come into physical contact with the host bone and form interconnected porous structure. However, there exists an accidental displacement of granules to unintended locations and leakage of granules from bone defects. Although covering the defect with a barrier membrane prevents granule emanation, this procedure is troublesome. To resolve these problems, we fabricated bioresorbable mesh cages (BRMc) in this study. Bone graft granules composed of carbonate apatite alone (Gr) and bioresorbable mesh cages (BRMc/Gr) introduced the bone graft granules and were implanted into the bone defect in the rabbit femur. Micro-computed tomography and histological analysis were conducted at 4 and 12 weeks after implantation. Osteoprogenitors in the bloodstream from the host bone passed through the pores of BRMc, penetrated the porous structure of graft granules, and might interact with individual granules. Then bone remodeling could progress actively and new bone was formed. The new bone formation was similar to the host bone at 12 weeks and there were minimal signs of local tissue inflammation. BRMc/Gr could reduce the risk of unwanted new bone formation occurring due to loss of granules from the bone defects compared with Gr because BRMc enclosed granules and prevent granules leakage from bone defects and BRMc could not induce unfavorable effects to forme new bone. Additionally, BRMc/Gr could keep granules assembled in one place, avoid displacement of granules to unintended locations, and carry easily. These results demonstrated that BRMc/Gr was effective in bone regeneration and improved clinical handling.


Subject(s)
Bone Transplantation , Femur , X-Ray Microtomography , Animals , Rabbits , Femur/surgery , Femur/diagnostic imaging , Femur/pathology , Bone Transplantation/methods , Absorbable Implants , Bone Regeneration , Osteogenesis/drug effects
6.
Stem Cell Res Ther ; 15(1): 144, 2024 May 20.
Article in English | MEDLINE | ID: mdl-38764077

ABSTRACT

BACKGROUND: The aim of this study was to evaluate potential synergistic effects of a single, local application of human umbilical cord MSC-derived sEVs in combination with a low dose of recombinant human rhBMP-2 to promote the regeneration of a metaphyseal femoral defect in an osteoporotic rat model. METHODS: 6 weeks after induction of osteoporosis by bilateral ventral ovariectomy and administration of a special diet, a total of 64 rats underwent a distal femoral metaphyseal osteotomy using a manual Gigli wire saw. Defects were stabilized with an adapted Y-shaped mini-locking plate and were subsequently treated with alginate only, or alginate loaded with hUC-MSC-sEVs (2 × 109), rhBMP-2 (1.5 µg), or a combination of sEVs and rhBMP-2 (n = 16 for each group). 6 weeks post-surgery, femora were evaluated by µCT, descriptive histology, and biomechanical testing. RESULTS: Native radiographs and µCT analysis confirmed superior bony union with callus formation after treatment with hUC-MSC-sEVs in combination with a low dose of rhBMP-2. This finding was further substantiated by histology, showing robust defect consolidation 6 weeks after treatment. Torsion testing of the explanted femora revealed increased stiffness after application of both, rhBMP-2 alone, or in combination with sEVs, whereas torque was only significantly increased after treatment with rhBMP-2 together with sEVs. CONCLUSION: The present study demonstrates that the co-application of hUC-MSC-sEVs can improve the efficacy of rhBMP-2 to promote the regeneration of osteoporotic bone defects.


Subject(s)
Bone Morphogenetic Protein 2 , Extracellular Vesicles , Femur , Osteoporosis , Recombinant Proteins , Umbilical Cord , Animals , Bone Morphogenetic Protein 2/pharmacology , Bone Morphogenetic Protein 2/genetics , Recombinant Proteins/pharmacology , Recombinant Proteins/genetics , Osteoporosis/pathology , Rats , Female , Humans , Femur/pathology , Femur/drug effects , Femur/diagnostic imaging , Umbilical Cord/cytology , Extracellular Vesicles/metabolism , Bone Regeneration/drug effects , Rats, Sprague-Dawley , Transforming Growth Factor beta/pharmacology , Disease Models, Animal , X-Ray Microtomography , Mesenchymal Stem Cells/metabolism
7.
Tomography ; 10(5): 816-825, 2024 May 20.
Article in English | MEDLINE | ID: mdl-38787022

ABSTRACT

BACKGROUND: Bone assessment using the MRI DEAL-IQ sequence may have the potential to serve as a substitute for evaluating bone strength by quantifying the bone marrow hematopoietic region (R2*) and marrow adiposity (proton density fat fraction: PDFF). Higher body mass index (BMI) is associated with increased bone mineral density (BMD) in the proximal femur; however, the relationship between BMI and R2* or PDFF remains unclear. Herein, we investigated the correlation between BMI and MRI IDEAL-IQ based R2* or PDFF of the proximal femur. METHODS: A retrospective single-cohort study was conducted on 217 patients diagnosed with non-metastatic prostate cancer between September 2019 and December 2022 who underwent MRI. The correlation between BMI and R2* or PDFF of the proximal femur was analyzed using Spearman's rank correlation test. RESULTS: Among 217 patients (median age, 74 years; median BMI, 23.8 kg/m2), there was a significant positive correlation between BMI and R2* at the right and left proximal femur (r = 0.2686, p < 0.0001; r = 0.2755, p < 0.0001, respectively). Furthermore, BMI and PDFF showed a significant negative correlation (r = -0.239, p = 0.0004; r = -0.2212, p = 0.001, respectively). CONCLUSION: In elderly men, the increased loading on the proximal femur due to elevated BMI was observed to promote a decrease in bone marrow adiposity in the proximal femur, causing a tendency for a transition from fatty marrow to red marrow with hematopoietic activity. These results indicate that the MRI IDEAL-IQ sequence may be valuable for assessing bone quality deterioration in the proximal femur.


Subject(s)
Body Mass Index , Bone Density , Femur , Magnetic Resonance Imaging , Humans , Male , Aged , Retrospective Studies , Magnetic Resonance Imaging/methods , Femur/diagnostic imaging , Femur/pathology , Bone Density/physiology , Aged, 80 and over , Prostatic Neoplasms/diagnostic imaging , Prostatic Neoplasms/pathology , Bone Marrow/diagnostic imaging , Bone Marrow/pathology , Adiposity , Middle Aged
8.
Int J Mol Sci ; 25(10)2024 May 09.
Article in English | MEDLINE | ID: mdl-38791213

ABSTRACT

Primary hip osteoarthritis (pOA) develops without an apparent underlying reason, whereas secondary osteoarthritis arises due to a known cause, such as developmental dysplasia of the hips (DDH-OA). DDH-OA patients undergo total hip arthroplasty at a much younger age than pOA patients (50.58 vs. 65 years in this study). Recently, mesenchymal stem and progenitor cells (MSPCs) have been investigated for the treatment of osteoarthritis due to their immunomodulatory and regenerative potential. This study identified cells in subchondral bone expressing common MSPC markers (CD10, CD73, CD140b, CD146, CD164, CD271, GD2, PDPN) in vivo and compared the proportions of these populations in pOA vs. DDH-OA, further correlating them with clinical, demographic, and morphological characteristics. The differences in subchondral morphology and proportions of non-hematopoietic cells expressing MSPC markers were noted depending on OA type and skeletal location. Bone sclerosis was more prominent in the pOA acetabulum (Ac) in comparison to the DDH-OA Ac and in the pOA Ac compared to the pOA femoral head (Fh). Immunophenotyping indicated diagnosis-specific differences, such as a higher proportion of CD164+ cells and their subsets in DDH-OA, while pOA contained a significantly higher proportion of CD10+ and GD2+ cells and subsets, with CD271+ being marginally higher. Location-specific differences showed that CD271+ cells were more abundant in the Fh compared to the Ac in DDH-OA patients. Furthermore, immunohistochemical characterization of stromal bone-adjacent cells expressing MSPC markers (CD10, CD164, CD271, GD2) in the Ac and Fh compartments was performed. This research proved that immunophenotype profiles and morphological changes are both location- and disease-specific. Furthermore, it provided potentially effective targets for therapeutic strategies. Future research should analyze the differentiation potential of subsets identified in this study. After proper characterization, they can be selectively targeted, thus enhancing personalized medicine approaches in joint disease management.


Subject(s)
Mesenchymal Stem Cells , Osteoarthritis, Hip , Humans , Mesenchymal Stem Cells/metabolism , Female , Male , Osteoarthritis, Hip/pathology , Osteoarthritis, Hip/etiology , Osteoarthritis, Hip/metabolism , Middle Aged , Aged , Acetabulum/pathology , Developmental Dysplasia of the Hip/metabolism , Developmental Dysplasia of the Hip/pathology , Adult , Biomarkers , Femur/pathology , Femur/metabolism , Immunophenotyping
9.
Mol Med Rep ; 30(2)2024 Aug.
Article in English | MEDLINE | ID: mdl-38818814

ABSTRACT

C1q/tumor necrosis factor­related protein 3 (CTRP3) expression is markedly reduced in the serum of patients with osteoporosis. The present study aimed to investigate whether CTRP3 reduces bone loss in oophorectomy (OVX)­induced mice via the AMP­activated protein kinase (AMPK)/sirtuin 1 (SIRT1)/nuclear factor E2­related factor 2 (Nrf2) signaling pathway. Female C57BL/6J mice and MC3T3­E1 cells were used to construct in vivo and in vitro models of osteoporosis, respectively. The left femurs of mice were examined using micro­computed tomography scans and bone­related quantitative morphological evaluation was performed. Pathological changes and the number of osteoclasts in the left femurs of mice were detected using hematoxylin and eosin, and tartrate­resistant acid phosphatase (TRAP) staining. Runt­related transcription factor­2 (RUNX2) expression in the left femurs was detected using immunofluorescence analysis, and the serum levels of bone resorption markers (C­telopeptide of type I collagen and TRAP) and bone formation markers [osteocalcin (OCN) and procollagen type 1 N­terminal propeptide] were detected. In addition, osteoblast differentiation and calcium deposits were examined in MC3T3­E1 cells using alkaline phosphatase (ALP) and Alizarin red staining, respectively. Moreover, RUNX2, ALP and OCN expression levels were detected using reverse transcription­quantitative PCR, and the expression levels of proteins associated with the AMPK/SIRT1/Nrf2 signaling pathway were detected using western blot analysis. The results revealed that globular CTRP3 (gCTRP3) alleviated bone loss and promoted bone formation in OVX­induced mice. gCTRP3 also facilitated the osteogenic differentiation of MC3T3­E1 cells through the AMPK/SIRT1/Nrf2 signaling pathway. The addition of an AMPK inhibitor (Compound C), SIRT1 inhibitor (EX527) or Nrf2 inhibitor (ML385) reduced the osteogenic differentiation of MC3T3­E1 cells via inhibition of gCTRP3. In conclusion, gCTRP3 inhibits OVX­induced osteoporosis by activating the AMPK/SIRT1/Nrf2 signaling pathway.


Subject(s)
AMP-Activated Protein Kinases , NF-E2-Related Factor 2 , Osteoporosis , Ovariectomy , Signal Transduction , Sirtuin 1 , Animals , Sirtuin 1/metabolism , Sirtuin 1/genetics , Female , Mice , Osteoporosis/metabolism , Osteoporosis/etiology , Osteoporosis/pathology , NF-E2-Related Factor 2/metabolism , Ovariectomy/adverse effects , AMP-Activated Protein Kinases/metabolism , Mice, Inbred C57BL , Osteoblasts/metabolism , Cell Line , Osteoclasts/metabolism , Disease Models, Animal , Femur/metabolism , Femur/pathology , Femur/diagnostic imaging , Osteogenesis/drug effects
10.
Cell Mol Biol (Noisy-le-grand) ; 70(3): 95-101, 2024 Mar 31.
Article in English | MEDLINE | ID: mdl-38650149

ABSTRACT

Osteoporosis is a common chronic bone disorder in postmenopausal women. Ginsenosides are primary active components in ginseng and the effects of various ginsenoside variants in osteoporosis treatment have been widely revealed. We planned to explore the impact of ginsenoside Rc on bone resorption in an osteoporosis rat model. We used ovariectomized rats to assess the potential impact of ginsenoside Rc on osteoporosis. µ-CT was implemented for analyzing the microstructure of the distal left femur in rats. H&E staining together with Masson staining were applied for bone histomorphometry evaluation. ELISA kits were implemented to detect serum concentrations of TRACP-5b, OCN, CTX, as well as PINP. Ginsenoside Rc treatment lessened the serum levels of TRACP-5b as well as CTX, while increasing serum levels of OCN, and PINP of OVX rats. Moreover, we found that ginsenoside Rc contributed to the synthesis of type I collagen via increasing Col1a1 and Col1a2 levels in femur tissues of ovariectomized rats. Our findings also revealed that ginsenoside Rc activated the TGF-ß/Smad pathway by increasing TGF-ß as well as phosphorylated Smad2/3 protein levels. Ginsenoside Rc alleviates osteoporosis in rats through promoting the TGF-ß/Smad pathway.


Subject(s)
Ginsenosides , Osteoporosis , Ovariectomy , Rats, Sprague-Dawley , Signal Transduction , Transforming Growth Factor beta , Ginsenosides/pharmacology , Ginsenosides/therapeutic use , Animals , Female , Osteoporosis/drug therapy , Osteoporosis/metabolism , Signal Transduction/drug effects , Transforming Growth Factor beta/metabolism , Femur/drug effects , Femur/metabolism , Femur/pathology , Smad Proteins/metabolism , Rats , Collagen Type I/metabolism , X-Ray Microtomography , Tartrate-Resistant Acid Phosphatase/metabolism , Osteocalcin/metabolism , Osteocalcin/blood , Disease Models, Animal , Procollagen/metabolism , Procollagen/blood
11.
Fetal Pediatr Pathol ; 43(3): 214-224, 2024.
Article in English | MEDLINE | ID: mdl-38587471

ABSTRACT

Fibrocartilaginous dysplasia (FCD) is a variant of fibrous dysplasia that often involves the proximal femur in young adults. It has a similar appearance on imaging as other entities but has stippled calcifications within the lesion. The differential diagnosis often includes benign and malignant tumors such as fibrous dysplasia, chondroblastoma, enchondroma, and chondrosarcoma. Histology is required for diagnosis and treatment is typically surgical due to the potential for pain, pathologic fracture, and deformity. We report the clinical presentation, imaging findings, and management of two pediatric patients with fibrocartilaginous dysplasia of the proximal femur to (1) highlight that recognition that fibrous dysplasia may contain cartilage upon frozen section will avoid overly aggressive therapy, and (2) FCD can occur in the McCune-Albright syndrome.


Subject(s)
Femur , Fibrous Dysplasia, Polyostotic , Humans , Fibrous Dysplasia, Polyostotic/diagnosis , Fibrous Dysplasia, Polyostotic/complications , Femur/pathology , Female , Male , Fractures, Spontaneous/etiology , Fractures, Spontaneous/diagnosis , Child , Diagnosis, Differential , Fibrous Dysplasia of Bone/diagnosis , Fibrous Dysplasia of Bone/complications , Fibrous Dysplasia of Bone/pathology
12.
BMJ Case Rep ; 17(4)2024 Apr 03.
Article in English | MEDLINE | ID: mdl-38569727

ABSTRACT

Malignant peripheral nerve sheath tumour (MPNST) is an aggressive soft tissue sarcoma with a poor prognosis, affecting most commonly the extremities. The lungs constitute the most frequent location for distant metastases. Half of all MPNSTs arise in patients with neurofibromatosis type 1, while approximately 10% are radiation induced and the rest are sporadic.The authors present a pregnant woman in her 40s with a sporadic MPNST of the lower limb and with lung metastases at diagnosis. Treatment consisted of interilioabdominal amputation, followed by adjuvant chemotherapy. Partial response and disease stabilisation were achieved with chemotherapy.Surgical resection with negative margins is the only potentially curative therapy, while radiation therapy and chemotherapy might be useful in the neoadjuvant or adjuvant setting, but their advantage in survival is not demonstrated. In the reported case, chemotherapy permitted the achievement of partial response and stabilisation of the disease.


Subject(s)
Fractures, Spontaneous , Nerve Sheath Neoplasms , Neurofibrosarcoma , Female , Pregnancy , Humans , Thigh/pathology , Nerve Sheath Neoplasms/complications , Nerve Sheath Neoplasms/surgery , Nerve Sheath Neoplasms/diagnosis , Pregnant Women , Femur/pathology
13.
An Acad Bras Cienc ; 96(3): e20230446, 2024.
Article in English | MEDLINE | ID: mdl-38655920

ABSTRACT

Pulmonary arterial hypertension (PAH) is characterized by right ventricular failure and diminished cardiac output, potentially leading to renal and bone impairments. In contrast, resistance exercise training (RT) offers cardiovascular and bone health benefits. This study aimed to assess the impacts of stable PAH induced by monocrotaline (MCT) and RT on renal morphometry, as well as bone morphometry and biomechanical properties in male Wistar rats. Four experimental groups, untrained control (UC, n=7), trained control (TC, n=7), untrained hypertensive (UH, n=7), trained hypertensive (TH, n=7), were defined. After the first MCT or saline injection (20 mg/kg), trained rats were submitted to a RT program (i.e., Ladder climbing), 5 times/week. Seven days later the rats received the second MCT or saline dose. After euthanasia, renal and femoral histomorphometry and femoral biomechanical properties were assessed. PAH reduced renal glomerular area and volume, which was prevented by the RT. While PAH did not harm the femoral morphometry, structural and mechanical properties, RT improved the femoral parameters (e.g., length, percentage of trabeculae and bone marrow, ultimte and yield loads). Experimental stable PAH promotes renal but not bone damages, whereas RT prevents renal deteriorations and improves the femoral morphological and biomechanical properties.


Subject(s)
Disease Models, Animal , Kidney , Monocrotaline , Physical Conditioning, Animal , Rats, Wistar , Resistance Training , Animals , Male , Physical Conditioning, Animal/physiology , Rats , Kidney/physiopathology , Kidney/pathology , Resistance Training/methods , Pulmonary Arterial Hypertension/physiopathology , Femur/pathology , Femur/physiopathology , Hypertension, Pulmonary/physiopathology , Hypertension, Pulmonary/chemically induced
14.
JBJS Case Connect ; 14(2)2024 Apr 01.
Article in English | MEDLINE | ID: mdl-38669356

ABSTRACT

CASE: Capitate avascular necrosis should be entertained in a differential diagnosis of young, active adults with midcarpal wrist pain. We present a case study of a 30-year-old laborer who developed avascular necrosis (AVN) of his right proximal capitate. Grip strength and wrist motion were limited on examination, with advanced imaging confirming AVN. A diagnostic arthroscopy confirmed the pathology. Treatment was completed with a medial femoral trochlea vascularized flap for cartilaginous resurfacing. At 10-month follow-up, the patient's capitate was healed with stable fixation, and he is working full-time as a laborer without restrictions. CONCLUSION: AVN of the capitate is a unique and challenging articular pathology that requires a thoughtful preoperative evaluation and meticulous surgical technique to reconstruct. The medial femoral trochlea (MFT) vascularized bone transfer with cartilaginous resurfacing is 1 available treatment option. This flap is harvested from the medial femur using microsurgical techniques, based on the descending genicular artery. Using a 2-surgeon approach, simultaneous dissection of the AVN is completed at the wrist. This flap is a vascularized option that can be used for both AVN and nonunion with structural deformity before salvage surgeries.


Subject(s)
Capitate Bone , Osteonecrosis , Surgical Flaps , Humans , Male , Adult , Osteonecrosis/surgery , Osteonecrosis/diagnostic imaging , Capitate Bone/surgery , Capitate Bone/diagnostic imaging , Surgical Flaps/blood supply , Femur/surgery , Femur/pathology , Femur/transplantation , Femur/blood supply
15.
Orthop Surg ; 16(4): 902-911, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38444378

ABSTRACT

OBJECTIVE: The best method for femoral fixation in anterior cruciate ligament reconstruction (ACLR) remains controversial. The study assesses the bone tunnel enlargement and clinical outcome in hamstring ACLR using cortical suspension or hybrid (cortical suspension and compression) femoral fixation. METHODS: From January 2010 to December 2021, 102 patients who underwent quadruple hamstring ACLR using cortical suspension (39 patients) or hybrid (63 patients) fixation on the femoral side were retrospectively analyzed. Clinical evaluation was conducted using the international knee documentation committee score, the Lysholm score, the Tegner activity level scale, the knee injury and osteoarthritis outcome score (quality of life score), the Lachman test, and the side-to-side difference by the KT-1000 arthrometer. The complications after the surgery were also evaluated. These data were compared at baseline and last follow-up. The diameters of the femoral tunnel were calculated at three sites: the width of the entrance of the femoral tunnel, 1 cm proximal to the entrance of the femoral tunnel and the largest diameter of the femoral tunnel on magnetic resonance imaging (MRI) coronal images. Bone tunnel widening data were contrasted between MRI images conducted at least 2 years and within 2 weeks after surgery. The morphology of bone tunnel enlargement was also observed and recorded. The categorical parameters were analyzed using the χ2-test and Fisher's exact test. The continuous variables conforming to a normal distribution were analyzed using Student's t-test, and the Mann-Whitney U-test was undertaken between the two groups without normal distribution. RESULTS: Both cortical suspension and hybrid femoral fixation in quadruple hamstring ACLR achieved significantly improved patient-reported outcome scores and knee stability compared to preoperative data. However, no significant differences were found between these two methods in clinical evaluations, postoperative complications, and patient-reported outcome scores. Although the mean diameter of the enlarged bone tunnel was lowered by an additional bioabsorbable interference screw fixation near the joint line, a statistically insignificant difference was found between the hybrid and cortical suspension fixation on the femoral side. There was no statistical difference in the distribution of enlarged bone tunnel morphology between groups. CONCLUSIONS: No significant difference was found in the bone tunnel enlargement and clinical outcome between cortical suspension and hybrid femoral fixation in ACLR using hamstring autograft.


Subject(s)
Anterior Cruciate Ligament Injuries , Anterior Cruciate Ligament Reconstruction , Hamstring Tendons , Humans , Anterior Cruciate Ligament , Retrospective Studies , Quality of Life , Hamstring Tendons/transplantation , Knee Joint/surgery , Femur/surgery , Femur/pathology , Anterior Cruciate Ligament Reconstruction/methods , Anterior Cruciate Ligament Injuries/surgery , Anterior Cruciate Ligament Injuries/pathology , Tibia/surgery
16.
Int Immunopharmacol ; 132: 111951, 2024 May 10.
Article in English | MEDLINE | ID: mdl-38552293

ABSTRACT

Cyclosporine A (CSA) is an immunosuppressant that has been extensively studied for its side effects on inhibiting osseointegration of titanium implants. However, the impact of CSA on bone healing in postmenopausal osteoporosis remains unknown. Therefore, this study aimed to investigate the effect of CSA on bone repair in an ovariectomized (OVX) rat model through both in vitro and in vivo experiments. We examined the interventions of CSA on osteoblast progenitor cells MC3T3-E1 and assessed their effects on biological function using RT-qPCR, CCK-8 assay, alizarin red staining, and alkaline phosphatase staining. Furthermore, we evaluated the effects of CSA on bone regeneration and bone mass in both OVX rat models and femoral diaphysis bone defect models. The results from the CCK-8 experiment indicated a positive influence of experimental doses of CSA on osteogenic differentiation of MC3T3-E1 cells. ALP expression levels and calcified nodules were also evaluated, suggesting that CSA intervention promoted osteogenic differentiation in MC3T3-E1 cells. Additionally, specific gene expressions including OPN, Runx-2, OC, and Col1a1 were up-regulated after CSA intervention. Biomechanical parameters aligned with histological analysis as well as micro-CT scans confirmed worse bone microstructure and strength following CSA intervention. Our findings preliminarily suggest that whether it is normal or osteoporotic bones, CSA has adverse effects on bone health which are associated with elevated-bone turnover.


Subject(s)
Bone Regeneration , Cell Differentiation , Cyclosporine , Disease Models, Animal , Osteoblasts , Osteogenesis , Ovariectomy , Rats, Sprague-Dawley , Animals , Bone Regeneration/drug effects , Female , Mice , Cyclosporine/pharmacology , Osteogenesis/drug effects , Osteoblasts/drug effects , Rats , Cell Differentiation/drug effects , Cell Line , Osteoporosis/drug therapy , Humans , Femur/drug effects , Femur/diagnostic imaging , Femur/pathology , Immunosuppressive Agents/pharmacology , Immunosuppressive Agents/therapeutic use , Osteoporosis, Postmenopausal/drug therapy
17.
Osteoarthritis Cartilage ; 32(6): 690-701, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38442768

ABSTRACT

OBJECTIVE: To investigate whether tibiofemoral alignment influences early knee osteoarthritis (OA). We hypothesized that varus overload exacerbates early degenerative osteochondral changes, and that valgus underload diminishes early OA. METHOD: Normal, over- and underload were induced by altering alignment via high tibial osteotomy in adult sheep (n = 8 each). Simultaneously, OA was induced by partial medial anterior meniscectomy. At 6 weeks postoperatively, OA was examined in five individual subregions of the medial tibial plateau using Kellgren-Lawrence grading, quantification of macroscopic OA, semiquantitative histopathological OA and immunohistochemical type-II collagen, ADAMTS-5, and MMP-13 scoring, biochemical determination of DNA and proteoglycan contents, and micro-computed tomographic evaluation of the subchondral bone. RESULTS: Multivariate analyses revealed that OA cartilaginous changes had a temporal priority over subchondral bone changes. Underload inhibited early cartilage degeneration in a characteristic topographic pattern (P ≥ 0.0983 vs. normal), in particular below the meniscal damage, avoided alterations of the subarticular spongiosa (P ≥ 0.162 vs. normal), and prevented the disturbance of otherwise normal osteochondral correlations. Overload induced early alterations of the subchondral bone plate microstructure towards osteopenia, including significantly decreased percent bone volume and increased bone surface-to-volume ratio (all P ≤ 0.0359 vs. normal). CONCLUSION: The data provide high-resolution evidence that tibiofemoral alignment modulates early OA induced by a medial meniscus injury in adult sheep. Since underload inhibits early OA, these data also support the clinical value of strategies to reduce the load in an affected knee compartment to possibly decelerate structural OA progression.


Subject(s)
Cartilage, Articular , Osteoarthritis, Knee , Tibia , Animals , Osteoarthritis, Knee/diagnostic imaging , Osteoarthritis, Knee/pathology , Sheep , Tibia/diagnostic imaging , Tibia/pathology , Cartilage, Articular/pathology , Cartilage, Articular/diagnostic imaging , Female , X-Ray Microtomography , Osteotomy , Femur/diagnostic imaging , Femur/pathology , Matrix Metalloproteinase 13/metabolism , Meniscectomy , Collagen Type II/metabolism , Menisci, Tibial/surgery , Menisci, Tibial/diagnostic imaging , Arthritis, Experimental/pathology , Arthritis, Experimental/diagnostic imaging , Disease Models, Animal , ADAMTS5 Protein/metabolism
18.
Knee Surg Sports Traumatol Arthrosc ; 32(6): 1363-1369, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38532466

ABSTRACT

PURPOSE: Trochlear dysplasia is one of the main risk factors for recurrent patellar dislocation. The Dejour classification identifies four categories that can be used to classify trochlear dysplasia. The purpose of this study is to evaluate the inter- and intraobserver reliability of the Dejour classification for trochlear dysplasia. The hypothesis was that both intra- and interobserver reliability would be at least moderate. METHODS: This is a cross-sectional, reliability study. Twenty-eight examiners from the International Patellofemoral Study Group 2022 meeting evaluated lateral radiographs of the knee and axial magnetic resonance images from 15 cases of patellofemoral instability with trochlear dysplasia. They classified each case according to Dejour's classification for trochlear dysplasia (A-D). There were three rounds: one with only computed radiograph (CR), one with only magnetic resonance imaging (MRI) and one with both. Inter- and intraobserver reliability were calculated using κ coefficient (0-1). RESULTS: The mean age of patients was: 14.6 years; 60% were female and 53% had open physis. The interobserver reliability κ probabilities were 0.2 (CR), 0.13 (MRI) and 0.12 (CR and MRI). The intraobserver reliability κ probabilities were 0.45 (CR), 0.44 (MRI) and 0.65 (CR and MRI). CONCLUSION: The Dejour classification for trochlear dysplasia has slight interobserver reliability and substantial intraobserver reliability. LEVEL OF EVIDENCE: Level I.


Subject(s)
Magnetic Resonance Imaging , Observer Variation , Patellofemoral Joint , Humans , Cross-Sectional Studies , Female , Reproducibility of Results , Adolescent , Male , Patellofemoral Joint/diagnostic imaging , Patellofemoral Joint/pathology , Patellar Dislocation/diagnostic imaging , Patellar Dislocation/classification , Joint Instability/classification , Joint Instability/diagnostic imaging , Tomography, X-Ray Computed , Femur/diagnostic imaging , Femur/pathology , Child
19.
Reumatol Clin (Engl Ed) ; 20(3): 162-165, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38443229

ABSTRACT

Gluteal pain is a frequent cause of medical attention in the daily clinical practice. It can be caused by multiple pathologies, being ischiofemoral impingement syndrome among those included in its differential diagnosis. Encompassed within the deep gluteal syndromes, this entity occurs as a consequence of the entrapment of the neuromuscular structures between the lesser femoral trochanter and the ischial tuberosity, causing pain in the root of the lower limb, with irradiation towards the thigh or the gluteal region and poor tolerance to deambulation and sedestation. The magnetic resonance imaging of the hip is fundamental for its diagnosis, and its management consists on medical treatment at onset. Despite not being a frequent diagnosis in the clinical practice in Rheumatology, keeping it in mind helps improving its prognosis by establishing an early and adequate treatment.


Subject(s)
Ischium , Musculoskeletal Pain , Humans , Ischium/diagnostic imaging , Ischium/pathology , Magnetic Resonance Imaging/methods , Femur/diagnostic imaging , Femur/pathology , Lower Extremity
20.
Sci Rep ; 14(1): 5867, 2024 03 11.
Article in English | MEDLINE | ID: mdl-38467756

ABSTRACT

To illustrate the surgical technique and explore clinical outcomes of the reconstruction for the malignant and metastatic bone tumour of proximal femur with metallic modular intercalary prosthesis. Sixteen patients who underwent modular intercalary prosthetic reconstruction after tumour resection were included from April 2012 and October 2020. Prosthesis and screws parameters, resected bone length and residual bone length, clinical outcomes and survivorship were analyzed. All patients were followed up for an average of 19 months (range 1-74). In our series, 12 patients died of the progression of the primary disease at the final follow-up. The cumulative survivorship since the treatment of proximal femoral metastasis was 78.6% (11 patients) at 6 months and 38.5% (5 patients) at 1 year. The mean MSTS score was 22.25 ± 4.55 among all patients. There were no cases of loosening or breakage of the prostheses, plates or screws, despite the various measurements of prostheses and residual bones. Modular intercalary prosthetic reconstruction was an effective method for malignant tumour of the proximal femur, including the advantages of providing early pain relief, quickly restoring postoperative function, required a short operation time, and preserving the adjacent joints.


Subject(s)
Bone Neoplasms , Femur , Humans , Treatment Outcome , Femur/pathology , Lower Extremity , Prosthesis Implantation/methods , Bone Neoplasms/pathology , Retrospective Studies
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