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1.
PLoS One ; 19(4): e0302215, 2024.
Article in English | MEDLINE | ID: mdl-38630735

ABSTRACT

OBJECTIVES: To determine the most appropriate method of functional assessment for "patellofemoral pain" (PFP)/"chondromalacia patella" for its diagnostic value, (validity, reliability, sensitivity, specificity, predictive value and clinical applicability); to outline initial interpretations of the questionnaires and their appropriateness, through the cut-off points determined in their scores based on physical test and Magnetic Resonance Imaging (MRI); to establish which methods should be used in conjunction with each other to obtain clinical diagnoses that are robust effective and efficient. METHODS: (1)Intra- and inter-observer reliability and of the relationship among PFP questionnaires/physical tests validated. (2)Predictive capacity of the questionnaires. Subject: 113 knees with PFP, assessed using "Knee-injury-and-Osteoarthritis Outcome-Score-for-Patellofemoral-pain-and-osteoarthritis" (KOOS-PF), "Kujala-Patellofemoral-Score" (KPS), "Victorian-Institute-of-Sports-Assessment-for-Patellar-tendons-questionnaire" (VISA-P), and the physical tests: "patellar-palpation", "patellar-tilt", "patellar-apprehension", "Clarke" and "squat". RESULTS: Questionnaires correlations themselves was 0.78

Subject(s)
Cartilage Diseases , Osteoarthritis , Patellofemoral Joint , Patellofemoral Pain Syndrome , Humans , Reproducibility of Results , Surveys and Questionnaires
2.
J Orthop Surg Res ; 19(1): 225, 2024 Apr 04.
Article in English | MEDLINE | ID: mdl-38576008

ABSTRACT

OBJECTIVE: This study was performed to investigate the effectiveness of two surgical procedures, autologous patellar tendon graft reconstruction and trans-tibial plateau pull-out repair, using a pig model. The primary focus was to assess the repair capability of medial meniscus posterior portion (MMPP) deficiency, the overall structural integrity of the meniscus, and protection of the femoral and tibial cartilage between the two surgical groups. The overall aim was to provide experimental guidelines for clinical research using these findings. METHODS: Twelve pigs were selected to establish a model of injury to the MMPP 10 mm from the insertion point of the tibial plateau. They were randomly divided into three groups of four animals each: reconstruction (autologous tendon graft reconstruction of the MMPP), pull-out repair (suture repair of the MMPP via a trans-tibial plateau bone tunnel), and control (use of a normal medial meniscus as the negative control). The animals were euthanized 12 weeks postoperatively for evaluation of the meniscus, assessment of tendon bone healing, and gross observation of knee joint cartilage. The tibial and femoral cartilage injuries were evaluated using the International Society for Cartilage Repair (ICRS) grade and Mankin score. Histological and immunohistochemical staining was conducted on the meniscus-tendon junction area, primary meniscus, and tendons. The Ishida score was used to evaluate the regenerated meniscus in the reconstruction group. Magnetic resonance imaging (MRI) was used to evaluate meniscal healing. RESULTS: All 12 pigs recovered well after surgery; all incisions healed without infection, and no obvious complications occurred. Gross observation revealed superior results in the reconstruction and pull-out repair groups compared with the control group. In the tibial cartilage, the reconstruction group had ICRS grade I injury whereas the pull-out repair and control groups had ICRS grade II and III injury, respectively. The Mankin score was significantly different between the reconstruction and control groups; histological staining showed that the structure of the regenerated meniscus in the reconstruction group was similar to that of the original meniscus. Immunohistochemical staining showed that the degree of type I and II collagen staining was similar between the regenerated meniscus and the original meniscus in the reconstruction group. The Ishida score was not significantly different between the regenerated meniscus and the normal primary meniscus in the reconstruction group. MRI showed that the MMPP in the reconstruction and pull-out repair groups had fully healed, whereas that in the control group had not healed. CONCLUSION: Autologous patellar tendon graft reconstruction of the MMPP can generate a fibrocartilage-like regenerative meniscus. Both reconstruction and pull-out repair can preserve the structural integrity of the meniscus, promote healing of the MMPP, delay meniscal degeneration, and protect the knee cartilage.


Subject(s)
Cartilage Diseases , Meniscus , Patellar Ligament , Phthalic Acids , Animals , Swine , Menisci, Tibial/diagnostic imaging , Menisci, Tibial/surgery , Patellar Ligament/diagnostic imaging , Patellar Ligament/surgery , Patellar Ligament/pathology , Meniscus/surgery , Cartilage Diseases/surgery
3.
Life Sci ; 346: 122630, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38614296

ABSTRACT

Bone remodeling is the balance between osteoblasts and osteoclasts. Bone diseases such as osteoporosis and osteoarthritis are associated with imbalanced bone remodeling. Skeletal injury leads to limited motor function and pain. Neurophilin was initially identified in axons, and its various ligands and roles in bone remodeling, angiogenesis, neuropathic pain and immune regulation were later discovered. Neurophilin promotes osteoblast mineralization and inhibits osteoclast differentiation and its function. Neuropolin-1 provides channels for immune cell chemotaxis and cytokine diffusion and leads to pain. Neuropolin-1 regulates the proportion of T helper type 17 (Th17) and regulatory T cells (Treg cells), and affects bone immunity. Vascular endothelial growth factors (VEGF) combine with neuropilin and promote angiogenesis. Class 3 semaphorins (Sema3a) compete with VEGF to bind neuropilin, which reduces angiogenesis and rejects sympathetic nerves. This review elaborates on the structure and general physiological functions of neuropilin and summarizes the role of neuropilin and its ligands in bone and cartilage diseases. Finally, treatment strategies and future research directions based on neuropilin are proposed.


Subject(s)
Bone Diseases , Neuropilins , Humans , Animals , Bone Diseases/metabolism , Bone Diseases/physiopathology , Neuropilins/metabolism , Neuropilins/physiology , Cartilage Diseases/metabolism , Cartilage Diseases/physiopathology , Bone Remodeling/physiology
4.
Foot Ankle Clin ; 29(2): 357-369, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38679445

ABSTRACT

The last several decades have brought about substantial development in our understanding of the biomolecular pathways associated with chondral disease and progression to arthritis. Within domains relevant to foot and ankle, genetic modification of stem cells, augmentation of bone marrow stimulation techniques, and improvement on existing scaffolds for delivery of orthobiologic agents hold promise in improving treatment of chondral injuries. This review summarizes novel developments in the understanding of the molecular pathways underlying chondral damage and some of the recent advancements within related therapeutics.


Subject(s)
Cartilage, Articular , Humans , Cartilage, Articular/injuries , Cartilage Diseases/therapy
5.
Foot Ankle Clin ; 29(2): 185-192, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38679432

ABSTRACT

The current concepts thoroughly highlight the ankle cartilage cascade focusing on the different stages and the different etiologic factors that can introduce a patient into the cascade. Moreover, the authors will provide the reader with a comprehensive overview of the types of lesions that may present as symptomatic, asymptomatic, and dangerous for progression into osteoarthritis, and the authors supply the reader with considerations and directions for future clinical implications and scientific endeavors.


Subject(s)
Ankle Injuries , Cartilage, Articular , Humans , Ankle Injuries/epidemiology , Ankle Injuries/pathology , Ankle Joint/pathology , Cartilage Diseases , Cartilage, Articular/pathology , Incidence , Osteoarthritis/etiology , Terminology as Topic
6.
BMJ Case Rep ; 17(4)2024 Apr 16.
Article in English | MEDLINE | ID: mdl-38627043

ABSTRACT

Nasal obstruction is a commonly reported issue in the Otorhinolaryngology Outpatient Department. In this case, an early adolescent boy with a long-standing problem of right-sided nasal obstruction since childhood sought consultation. Diagnostic nasal endoscopy revealed a deviation of the nasal septum to the left, coupled with right inferior turbinate hypertrophy, all overlying healthy mucosa. A CT scan of the nose and paranasal sinuses further identified a bony hyperdense lesion with ground glass attenuation, confined to the right inferior turbinate. Subsequent biopsy confirmed juvenile trabecular ossifying fibroma (JTOF). The patient underwent endoscopic right medial maxillectomy, and the final histology affirmed the diagnosis of JTOF.


Subject(s)
Bone Neoplasms , Cartilage Diseases , Fibroma, Ossifying , Nasal Obstruction , Paranasal Sinuses , Male , Adolescent , Humans , Child , Turbinates/diagnostic imaging , Turbinates/surgery , Turbinates/pathology , Fibroma, Ossifying/diagnostic imaging , Fibroma, Ossifying/surgery , Nasal Obstruction/diagnostic imaging , Nasal Obstruction/etiology , Nasal Obstruction/pathology , Bone Neoplasms/pathology , Cartilage Diseases/pathology
7.
Foot Ankle Clin ; 29(2): 253-263, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38679437

ABSTRACT

Biological agents like growth factors (ie, platelet rich plasma) and mesenchymal stem cells are rising in popularity among orthopedics. Orthobiologics therapy aims to fill the gap between conventional conservative therapies like hyaluronic acid and surgery, especially for cartilage disease. Ankle cartilage defects are very symptomatic and could lead to a severe decrease of quality of life in patients, because of pain, swelling, and inability to walk without pain. In this scenario, this paper aims to systematically review the current literature available about biological therapies for ankle cartilage.


Subject(s)
Ankle Joint , Cartilage, Articular , Conservative Treatment , Humans , Cartilage Diseases/therapy , Mesenchymal Stem Cell Transplantation , Platelet-Rich Plasma
8.
J Pediatr Orthop ; 44(5): e457-e462, 2024.
Article in English | MEDLINE | ID: mdl-38477312

ABSTRACT

BACKGROUND: Despite the fact that meniscocapsular anterior detachment is the most common location of instability in children with a Discoid Lateral Meniscus (DLM), there is a lack of consensus about the type of repair that should be utilized for stabilization. The aim of this study was to determine the best fixation method for anterior detachment of DLM in children. Our hypothesis was that excessive rigidity with fixation would restrict meniscal mobility and increase the rate of failure or prevent full knee flexion. METHODS: This study was a retrospective single-center study consisting of 51 consecutive knees (45 children) with menico-capsular anterior detachment that underwent stabilization and minimal saucerization of the meniscus between 2007 and 2018. We aimed to compare the need for revision surgery and knee flexion between the different types of fixations utilized; namely we compared meniscopexy using anchors on the tibia (n=30) with outside-in arthroscopic soft tissue fixation (n=21), and absorbable (n=18) and nonabsorbable sutures (n=33) were compared. RESULTS: The mean age at surgery was 10.4 years (3 to 17) with a mean follow-up of 52 months (18 to 148). The group of knees treated with absorbable sutures had a significantly better rate of full knee flexion (15/18) compared with the nonabsorbable group (17/33) ( P =0.03). Despite the absence of significance ( P =007), there was a lower rate of revision surgery due to suture failure in the soft tissue fixation group (0 revision operations) compared with the meniscopexy group (5 revision operations). CONCLUSIONS: For anterior meniscocapsular detachment of DLM, it is recommended to perform soft tissue fixation with absorbable sutures, as this technique resulted in better knee flexion and a lower rate of revision surgery when compared with meniscopexy and nonabsorbable suture fixation. LEVEL OF EVIDENCE: Level III-retrospective case studies.


Subject(s)
Cartilage Diseases , Joint Diseases , Child , Humans , Menisci, Tibial/surgery , Retrospective Studies , Tibia/surgery , Sutures , Arthroscopy/methods , Knee Joint/surgery
9.
Int J Mol Sci ; 25(6)2024 Mar 12.
Article in English | MEDLINE | ID: mdl-38542208

ABSTRACT

Mucopolysaccharidosis type IVA (MPS IVA; Morquio A syndrome) is a rare autosomal recessive lysosomal storage disease (LSD) caused by deficiency of a hydrolase enzyme, N-acetylgalactosamine-6-sulfate sulfatase, and characterized clinically by mainly musculoskeletal manifestations. The mechanisms underlying bone involvement in humans are typically explored using invasive techniques such as bone biopsy, which complicates analysis in humans. We compared bone proteomes using DDA and SWATH-MS in wild-type and MPS IVA knockout mice (UNT) to obtain mechanistic information about the disease. Our findings reveal over 1000 dysregulated proteins in knockout mice, including those implicated in oxidative phosphorylation, oxidative stress (reactive oxygen species), DNA damage, and iron transport, and suggest that lactate dehydrogenase may constitute a useful prognostic and follow-up biomarker. Identifying biomarkers that reflect MPS IVA clinical course, severity, and progression have important implications for disease management.


Subject(s)
Bone Diseases , Cartilage Diseases , Chondroitinsulfatases , Mucopolysaccharidosis IV , Humans , Animals , Mice , Mucopolysaccharidosis IV/metabolism , Chondroitinsulfatases/genetics , Mice, Knockout
10.
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi ; 38(3): 272-277, 2024 Mar 15.
Article in Chinese | MEDLINE | ID: mdl-38500418

ABSTRACT

Objective: To discuss the application of anterior region suture of the popliteal hiatus (PH) under arthroscopy in the treatment of discoid lateral meniscus (DLM) injury with instability in the popliteal tendon region. Methods: The clinical data of 53 patients (56 knees) with DLM injury who met the selection criteria between March 2014 and November 2022 were retrospectively analyzed. There were 15 males and 38 females, aged 8-55 years with an average age of 36.5 years. Fourteen cases had a history of trauma, while the remaining 39 cases had no clear history of trauma. The disease duration ranged from 1 day to 6 years, with an average duration of 15.6 months. According to the Watanabe classification, there were 40 knees of complete type and 16 knees of incomplete type. The preoperative International Knee Documentation Committee (IKDC) knee joint score was 51.2±8.3, the Lysholm score was 59.6±11.2, and the visual analogue scale (VAS) score was 4.7±1.3. After the arthroscopic meniscal plasty, the instability of the popliteal tendon region meniscus was checked by probing traction. Subsequently, the Out-inside technique or a combination of Out-inside and All-inside techniques was used to suture the anterior region of the PH. The stability of the meniscus after suturing was assessed, and if necessary, further suturing using the All-inside technique at the posterior region of the PH, the posterior horn of the meniscus, and using the Out-inside technique at the anterior horn of the meniscus was performed. Postoperative complications were recorded. The effectiveness was evaluated using pre- and post-operative IKDC scores, Lysholm scores, and VAS scores. Results: After operation, knee joint pain, crepitus, and locking disappeared, with McMurray and grinding tests turning negative. All patients were followed up 12-93 months with an average of 57.5 months. There was no complication such as common peroneal nerve injury, deep vein thrombosis of the lower limbs, joint infection, or joint stiffness. At last follow-up, the IKDC knee joint score was 76.7±5.5, the Lysholm score was 94.0±4.1, and the VAS score was 1.1±0.8. The differences compared with preoperative scores were significant ( t=-22.090, P<0.001; t=-23.704, P<0.001; t=19.767, P<0.001). Conclusion: Suturing of the anterior region of the PH is crucial in the treatment of DLM injury with instability in the popliteal tendon region.


Subject(s)
Cartilage Diseases , Tibial Meniscus Injuries , Male , Female , Humans , Adult , Menisci, Tibial/surgery , Follow-Up Studies , Retrospective Studies , Tibial Meniscus Injuries/surgery , Knee Joint/surgery , Lower Extremity , Arthroscopy/methods , Sutures , Treatment Outcome
11.
J Cell Mol Med ; 28(7): e18242, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38509736

ABSTRACT

Articular cartilage defect is challenged by insufficient regenerative ability of cartilage. Catalpol (CA), the primary active component of Rehmanniae Radix, could exert protective effects against various diseases. However, the impact of CA on the treatment of articular cartilage injuries is still unclear. In this study, full-thickness articular cartilage defect was induced in a mouse model via surgery. The animals were intraperitoneally injected with CA for 4 or 8 weeks. According to the results of macroscopic observation, micro-computed tomography CT (µCT), histological and immunohistochemistry staining, CA treatment could promote mouse cartilage repair, resulting in cartilage regeneration, bone structure improvement and matrix anabolism. Specifically, an increase in the expression of CD90, the marker of mesenchymal stem cells (MSCs), in the cartilage was observed. In addition, we evaluated the migratory and chondrogenic effects of CA on MSCs. Different concentration of CA was added to C3H10 T1/2 cells. The results showed that CA enhanced cell migration and chondrogenesis without affecting proliferation. Collectively, our findings indicate that CA may be effective for the treatment of cartilage defects via stimulation of endogenous MSCs.


Subject(s)
Cartilage Diseases , Cartilage, Articular , Iridoid Glucosides , Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells , Animals , Mice , Cartilage, Articular/pathology , X-Ray Microtomography , Cell Differentiation , Cartilage Diseases/metabolism , Mesenchymal Stem Cell Transplantation/methods , Chondrogenesis
12.
Sci Rep ; 14(1): 5310, 2024 03 04.
Article in English | MEDLINE | ID: mdl-38438474

ABSTRACT

Our study aimed to compare bone scintigraphy and dual-layer detector spectral CT (DLCT) with multiphase contrast enhancement for the diagnosis of osteoblastic bone lesions in patients with prostate cancer. The patients with prostate cancer and osteoblastic bone lesions detected on DLCT were divided into positive bone scintigraphy group (pBS) and negative bone scintigraphy group (nBS) based on bone scintigraphy. A total of 106 patients (57 nBS and 49 pBS) was included. The parameters of each lesion were measured from DLCT including Hounsfield unit (HU), 40-140 keV monochromatic HU, effective nuclear numbers (Zeff), and Iodine no water (InW) value in non-contrast phase (N), the arterial phase (A), and venous phase (V). The slope of the spectral curve at 40 and 100 keV, the different values of the parameters between A and N phase (A-N), V and N phase (V-N), and hybrid prediction model with multiparameters were used to differentiate pBS from nBS. Receiver operating characteristic analysis was performed to compare the area under the curve (AUC) for differentiating the pBS group from the nBS group. The value of conventional HU values, slope, and InW in A-N and V-N, and hybrid model were significantly higher in the pBS group than in the nBS group. The hybrid model of all significant parameters had the highest AUC of 0.988, with 95.5% sensitivity and 94.6% specificity. DLCT with arterial contrast enhancement phase has the potential to serve as an opportunistic screening tool for detecting positive osteoblastic bone lesions, corresponding to those identified in bone scintigraphy.


Subject(s)
Bone Diseases , Cartilage Diseases , Iodine , Prostatic Neoplasms , Male , Humans , Early Detection of Cancer , Tomography, X-Ray Computed , Mass Screening , Prostatic Neoplasms/diagnostic imaging , Radionuclide Imaging
13.
Orthop Surg ; 16(5): 1187-1195, 2024 May.
Article in English | MEDLINE | ID: mdl-38488230

ABSTRACT

OBJECTIVE: The decision on whether or not and how to treat a local cartilage defect is still made intraoperatively based on the visual presentation of the cartilage and findings from indentations with an arthroscopic probe. The treatment decision is then usually based on grading according to established classifications systems, which, therefore, need to have high reliability and accuracy. The aim of the present study was to evaluate the reliability and accuracy of the Outerbridge classification in staging cartilage defects. METHODS: We performed an observer arthroscopic study using the Outerbridge classification on seven fresh-frozen human cadaveric knees, which collectively exhibited nine cartilage defects. To evaluate accuracy, defect severity was verified through histological examination. Interrater and intrarater reliabilites were calculated using Cohen's kappa and the intra-class correlation coefficient (ICC 3.1). RESULTS: The interrater and intrarater reliability for the Outerbridge classification ranged from poor to substantial, with 0.24 ≤ κ ≤ 0.70 and κ = 0.55 to κ = 0.66, respectively. The accuracy evaluated by comparison with the histological examination was 63% overall. The erroneous evaluations were, however, still often at the discrimination of grade 2 and 3. We did not find any relationship between higher experience and accuracy or intraobserver reliability. Taken together, these results encourage surgeons to further use diagnostic arthroscopy for evaluating cartilage lesions. Nevertheless, especially in grade 2 and 3, deviations from the histology were observed. This is, however, the point where a decision is made on whether to surgically address the defect or not. CONCLUSION: Diagnostic arthroscopy is the standard for cartilage lesion assessment, yet interobserver reliability is fair to substantial. Caution is warranted in interpreting varied observer results. The accuracy of the "simpler" Outerbridge classification is insufficient compared to histological examinations, highlighting the need for improved techniques in guideline-based intraoperative decision-making.


Subject(s)
Arthroscopy , Cadaver , Cartilage, Articular , Observer Variation , Humans , Reproducibility of Results , Arthroscopy/methods , Cartilage, Articular/pathology , Cartilage, Articular/surgery , Aged , Male , Female , Cartilage Diseases/pathology , Middle Aged
14.
Int Orthop ; 48(6): 1627-1634, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38502336

ABSTRACT

PURPOSE: Idiopathic chondrolysis of the hip is characterized by the loss of the articular cartilage of the hip joint with spectrum ranging from full recovery to fibrous ankylosis. Study assessed outcomes following intra-articular steroid injections, joint manipulation and traction immobilization. METHODS: Retrospective (2012-2021) review of 41 cases treated for idiopathic chondrolysis of hip, assessed pre-operatively and post-operatively (minimum 2-year follow-up) using Children's Hospital Oakland Hip Evaluation Score (CHOHES), visual analogue scale (VAS) and range of motion measurements. RESULTS: Twenty-five patients (62%) achieved painless mobility, 6 (14%) had hip stiffness without pain and 10 (24%) had painful and stiff hips at final follow-up. They had a mean age of 12.49 ± 2.4 years and a mean follow-up duration of 33.15 ± 13.1 months. Range of motion improved significantly (p < 0.05). VAS improved to 3.93 ± 1.3 from 7.8 ± 0.7. CHOHES improved from 29.12 ± 9.9 to 56.37 ± 17.6. CONCLUSION: Intra-articular steroid injection, manipulation and traction immobilization may effectively treat idiopathic chondrolysis of the hip by enhancing patient function and reducing the need for further surgical intervention.


Subject(s)
Cartilage Diseases , Cartilage, Articular , Hip Joint , Range of Motion, Articular , Humans , Female , Retrospective Studies , Male , Child , Hip Joint/surgery , Hip Joint/physiopathology , Adolescent , Cartilage Diseases/therapy , Cartilage Diseases/surgery , Injections, Intra-Articular , Cartilage, Articular/surgery , Treatment Outcome , Traction/methods
15.
Arthritis Res Ther ; 26(1): 66, 2024 Mar 11.
Article in English | MEDLINE | ID: mdl-38468277

ABSTRACT

BACKGROUND: CRISPR-Cas9-based genome engineering represents a powerful therapeutic tool for cartilage tissue engineering and for understanding molecular pathways driving cartilage diseases. However, primary chondrocytes are difficult to transfect and rapidly dedifferentiate during monolayer (2D) cell culture, making the lengthy expansion of a single-cell-derived edited clonal population not feasible. For this reason, functional genetics studies focused on cartilage and rheumatic diseases have long been carried out in cellular models that poorly recapitulate the native molecular properties of human cartilaginous tissue (e.g., cell lines, induced pluripotent stem cells). Here, we set out to develop a non-viral CRISPR-Cas9, bulk-gene editing method suitable for chondrocyte populations from different cartilaginous sources. METHODS: We screened electroporation and lipid nanoparticles for ribonucleoprotein (RNP) delivery in primary polydactyly chondrocytes, and optimized RNP reagents assembly. We knocked out RELA (also known as p65), a subunit of the nuclear factor kappa B (NF-κB), in polydactyly chondrocytes and further characterized knockout (KO) cells with RT-qPCR and Western Blot. We tested RELA KO in chondrocytes from diverse cartilaginous sources and characterized their phenotype with RT-qPCR. We examined the chondrogenic potential of wild-type (WT) and KO cell pellets in presence and absence of interleukin-1ß (IL-1ß). RESULTS: We established electroporation as the optimal transfection technique for chondrocytes enhancing transfection and editing efficiency, while preserving high cell viability. We knocked out RELA with an unprecedented efficiency of ~90%, confirming lower inflammatory pathways activation upon IL-1ß stimulation compared to unedited cells. Our protocol could be easily transferred to primary human chondrocytes harvested from osteoarthritis (OA) patients, human FE002 chondroprogenitor cells, bovine chondrocytes, and a human chondrocyte cell line, achieving comparable mean RELA KO editing levels using the same protocol. All KO pellets from primary human chondrocytes retained chondrogenic ability equivalent to WT cells, and additionally displayed enhanced matrix retention under inflamed conditions. CONCLUSIONS: We showcased the applicability of our bulk gene editing method to develop effective autologous and allogeneic off-the-shelf gene therapies strategies and to enable functional genetics studies in human chondrocytes to unravel molecular mechanisms of cartilage diseases.


Subject(s)
Cartilage Diseases , Polydactyly , Humans , Animals , Cattle , Chondrocytes/metabolism , Gene Editing/methods , CRISPR-Cas Systems/genetics , Interleukin-1beta/metabolism , Cartilage Diseases/metabolism , Polydactyly/metabolism
16.
Osteoarthritis Cartilage ; 32(5): 535-547, 2024 May.
Article in English | MEDLINE | ID: mdl-38403152

ABSTRACT

OBJECTIVE: The subchondral bone is an emerging regulator of osteoarthritis (OA). However, knowledge of how specific subchondral alterations relate to cartilage degeneration remains incomplete. METHOD: Femoral heads were obtained from 44 patients with primary OA during total hip arthroplasty and from 30 non-OA controls during autopsy. A multiscale assessment of the central subchondral bone region comprising histomorphometry, quantitative backscattered electron imaging, nanoindentation, and osteocyte lacunocanalicular network characterization was employed. RESULTS: In hip OA, thickening of the subchondral bone coincided with a higher number of osteoblasts (controls: 3.7 ± 4.5 mm-1, OA: 16.4 ± 10.2 mm-1, age-adjusted mean difference 10.5 mm-1 [95% CI 4.7 to 16.4], p < 0.001) but a similar number of osteoclasts compared to controls (p = 0.150). Furthermore, higher matrix mineralization heterogeneity (CaWidth, controls: 2.8 ± 0.2 wt%, OA: 3.1 ± 0.3 wt%, age-adjusted mean difference 0.2 wt% [95% CI 0.1 to 0.4], p = 0.011) and lower tissue hardness (controls: 0.69 ± 0.06 GPa, OA: 0.67 ± 0.06 GPa, age-adjusted mean difference -0.05 GPa [95% CI -0.09 to -0.01], p = 0.032) were detected. While no evidence of altered osteocytic perilacunar/canalicular remodeling in terms of fewer osteocyte canaliculi was found in OA, specimens with advanced cartilage degeneration showed a higher number of osteocyte canaliculi and larger lacunocanalicular network area compared to those with low-grade cartilage degeneration. Multiple linear regression models indicated that several subchondral bone properties, especially osteoblast and osteocyte parameters, were closely related to cartilage degeneration (R2 adjusted = 0.561, p < 0.001). CONCLUSION: Subchondral bone properties in OA are affected at the compositional, mechanical, and cellular levels. Based on their strong interaction with cartilage degeneration, targeting osteoblasts/osteocytes may be a promising therapeutic OA approach. DATA AND MATERIALS AVAILABILITY: All data are available in the main text or the supplementary materials.


Subject(s)
Cartilage Diseases , Cartilage, Articular , Osteoarthritis, Hip , Humans , Osteoblasts , Osteocytes
17.
Knee Surg Sports Traumatol Arthrosc ; 32(3): 636-644, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38391111

ABSTRACT

PURPOSE: Viable cartilage allograft (VCA) is a cartilage tissue matrix that contains cryopreserved viable allogeneic cartilage fibres. This study aimed to assess safety and benefits in treating focal knee cartilage defects with VCA. We hypothesized that VCA is a safe single-stage procedure in isolated chondral defects. METHOD: In vitro analysis, in vivo studies and a prospective case series were performed. VCA was evaluated in a goat cartilage repair model. Symptomatic International Cartilage Repair Society grade 3/4A lesions of the femoral condyle or patella were implanted with VCA. International Knee Documentation Committee (IKDC), Knee injury and Osteoarthritis Outcome (KOOS) subscales, Lysholm, Short Form-12, Visual Analog Scale and pain frequency levels were assessed. Radiographic and magnetic resonance imaging (MRI) was performed at regular intervals postoperatively. Data were analysed by statisticians to determine the power and significance of the results. RESULTS: The goat study confirmed that VCA is effective for cartilage repair. Twenty patients were implanted; the mean age was 28.1 (16-56), the mean body mass index (BMI) was 27.9 ± 5.6 and the mean follow-up was 24.1 months (range = 12.0-36.0 months). Lesions were in either the femoral condyle (7) or patella (13). Lesion sizes ranged from 1.5 to 6.0 cm2 (mean = 4.58 cm2 ). Outcome scores improved from preoperative baseline (POB): IKDC (78.2), Lysholm (89.0), KOOS: Pain (95.8), Symptoms (86.3), ADL (87.8), Sports (85.0) and QOL (75.0). MRI imaging demonstrated excellent osteochondral allograft assimilation. Second-look arthroscopy (two patients) demonstrated complete fill and incorporation (Brittberg scores 11/12). Functional scores were maintained at 24 (M): IKDC (86.24 ± 17.2), Lysholm (87.23 ± 15.0), KOOS: Pain (91.72 ± 17.3), Symptoms (84.92 ± 16.1), ADLs (93.80 ± 16.1), Sports (84.45 ± 27.7), QOL (81.30 ± 20.8). CONCLUSION: VCA is an off-the-shelf, single-stage, conformable allogeneic graft that treats chondral defects with no additional fixation. Preclinical and short-term prospective clinical studies show that VCA can safely treat chondral defects with potential advantages to existing options. LEVEL OF EVIDENCE: Level IV study.


Subject(s)
Cartilage Diseases , Cartilage, Articular , Knee Injuries , Osteoarthritis, Knee , Humans , Animals , Adult , Cartilage, Articular/surgery , Quality of Life , Treatment Outcome , Knee Joint/surgery , Cartilage Diseases/pathology , Magnetic Resonance Imaging , Osteoarthritis, Knee/pathology , Knee Injuries/surgery , Allografts , Pain/pathology , Goats , Follow-Up Studies
18.
Tomography ; 10(2): 243-254, 2024 Feb 11.
Article in English | MEDLINE | ID: mdl-38393287

ABSTRACT

PURPOSE: To evaluate magnetic resonance image (MRI) findings in children and adolescents suffering from knee pain without traumatic or physical overload history and to identify potential anatomic risk factors. MATERIAL AND METHODS: A total of 507 MRIs of 6- to 20-year-old patients (251 males; 256 females) were evaluated with regard to detectable pathologies of the knee. The results were compared to a control group without pain (n = 73; 34 males; 39 females). A binary logistic regression model and t-tests for paired and unpaired samples were used to identify possible risk factors and significant anatomic differences of the study population. RESULTS: In 348 patients (68.6%), at least one pathology was detected. The most commonly detected finding was chondromalacia of the patellofemoral (PF) joint (n = 205; 40.4%). Chondral lesions of the PF joint occurred significantly more often in knee pain patients than in the control group (40% vs. 11.0%; p = 0.001), especially in cases of a patella tilt angle > 5° (p ≤ 0.001), a bony sulcus angle > 150° (p = 0.002), a cartilaginous sulcus angle > 150° (p = 0.012), a lateral trochlear inclination < 11° (p ≤ 0.001), a lateralised patella (p = 0.023) and a Wiberg type II or III patella shape (p = 0.019). Moreover, a larger patella tilt angle (p = 0.021), a greater bony sulcus angle (p = 0.042), a larger cartilaginous sulcus angle (p = 0.038) and a lower value of the lateral trochlear inclination (p = 0.014) were detected in knee pain patients compared to the reference group. CONCLUSION: Chondromalacia of the PF joint is frequently observed in children and adolescents suffering from non-overload atraumatic knee pain, whereby a patella tilt angle > 5°, a bony sulcus angle > 150°, a cartilaginous sulcus angle > 150°, a lateral trochlear inclination < 11°, a lateralised patella and a Wiberg type II or III patella shape seem to represent anatomic risk factors.


Subject(s)
Cartilage Diseases , Patellofemoral Joint , Male , Child , Female , Humans , Adolescent , Young Adult , Adult , Patellofemoral Joint/diagnostic imaging , Patellofemoral Joint/pathology , Magnetic Resonance Imaging , Cartilage Diseases/pathology , Pain/diagnostic imaging , Pain/pathology , Risk Factors
19.
Arch Orthop Trauma Surg ; 144(4): 1655-1665, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38206448

ABSTRACT

INTRODUCTION: The aim of the present study was to evaluate midterm outcomes 5-7 years after matrix-associated autologous chondrocyte implantation (MACI) in the patellofemoral joint. MATERIALS AND METHODS: Twenty-six patients who had undergone MACI using the Novocart® 3D scaffold were prospectively evaluated. Clinical outcomes were determined by measuring the 36-Item Short-Form Health Survey (SF-36) and International Knee Documentation Committee (IKDC) scores and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) values preoperatively and 3, 6, and 12 months, and a mean of 6 years postoperatively. At the final follow-up, the Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) score was evaluated. RESULTS: Twenty-two patients with 23 focal cartilage defects (19 patella and four trochlea) were available for the final follow-up. The mean defect size was 4.0 ± 1.9 cm2 (range 2.4-9.4 cm2). All clinical outcome scores improved significantly until 5-7 years after MACI (SF-36 score, 61.2 ± 19.6 to 83.2 ± 11.6; P = 0.001; IKDC score, 47.5 ± 20.6 to 74.7 ± 15.5; P < 0.001; and WOMAC, 29.8 ± 15.7 to 8.2 ± 10.3; P < 0.001). The mean MOCART score was 76.0 ± 11.0 at the final follow-up. Nineteen of the 22 patients (86.4%) were satisfied with the outcomes after 5-7 years and responded that they would undergo the procedure again. CONCLUSION: MACI in the patellofemoral joint demonstrated good midterm clinical results with a significant reduction in pain, improvement in function, and high patient satisfaction. These clinical findings are supported by radiological evidence from MOCART scores. LEVEL OF EVIDENCE: IV-case series.


Subject(s)
Cartilage Diseases , Cartilage, Articular , Knee Injuries , Patellofemoral Joint , Humans , Patellofemoral Joint/diagnostic imaging , Patellofemoral Joint/surgery , Chondrocytes , Follow-Up Studies , Cartilage, Articular/diagnostic imaging , Cartilage, Articular/surgery , Knee Injuries/surgery , Transplantation, Autologous/methods , Cartilage Diseases/surgery , Knee Joint/surgery , Magnetic Resonance Imaging , Pain
20.
Mater Horiz ; 11(6): 1465-1483, 2024 03 18.
Article in English | MEDLINE | ID: mdl-38221872

ABSTRACT

Osteoarthritis (OA) is a common joint disease known for cartilage degeneration, leading to a substantial burden on individuals and society due to its high disability rate. However, current clinical treatments for cartilage defects remain unsatisfactory due to the unclear mechanisms underlying cartilage regeneration. Tissue engineering hydrogels have emerged as an attractive approach in cartilage repair. Recent research studies have indicated that stem cells can sense the mechanical strength of hydrogels, thereby regulating their differentiation fate. In this study, we present the groundbreaking construction of dual-network DNA-silk fibroin (SF) hydrogels with controllable surface rigidity. The supramolecular networks, formed through DNA base-pairing, induce the development of ß-sheet structures by constraining and aggregating SF molecules. Subsequently, SF was cross-linked via horseradish peroxidase (HRP)-mediated enzyme reactions to form the second network. Experimental results demonstrated a positive correlation between the surface rigidity of dual-network DNA-SF hydrogels and the DNA content. Interestingly, it was observed that dual-network DNA-SF hydrogels with moderate surface rigidity exhibited the highest effectiveness in facilitating the migration of bone marrow mesenchymal stem cells (BMSCs) and their chondrogenic differentiation. Transcriptome sequencing further confirmed that dual-network DNA-SF hydrogels primarily enhanced chondrogenic differentiation of BMSCs by upregulating the Wnt and TGF-ß signaling pathways while accelerating collagen II synthesis. Furthermore, in vivo studies revealed that dual-network DNA-SF hydrogels with moderate surface rigidity significantly accelerated cartilage regeneration. In summary, the dual-network DNA-SF hydrogels represent a promising and novel therapeutic strategy for cartilage regeneration.


Subject(s)
Cartilage Diseases , Fibroins , Humans , Fibroins/chemistry , Hydrogels , Cartilage/physiology , Tissue Engineering/methods , Cell Differentiation/genetics
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