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1.
Yonago Acta Med ; 67(1): 22-30, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38371277

ABSTRACT

Background: This study aimed to evaluate the effect of chitin nanofibers (CNF) produced from crab shells as a medical material for the knee in an osteoarthritic rat model. Methods: The effect of intra-articular CNF injection was evaluated histologically among three groups: saline, hyaluronic acid (HA), and CNF injection groups. The Osteoarthritis Research Society International (OARSI) cartilage, subchondral bone, synovial, and meniscus scores were used for scoring. Results: At 4 weeks, the CNF group had significantly lower scores than the saline group. The Synovial score was lower in HA and CNF groups at 4 weeks than in the saline group. At 4 weeks post-treatment, the thickening of the subchondral bone plate and angiogenesis were significantly reduced in the CNF treatment group compared to those in the saline treatment group (P = 0.02). Conclusion: The anti-inflammatory effects of CNF on knee osteoarthritis were comparable to that of HA in the early stages.

2.
Mod Rheumatol ; 2024 Jan 19.
Article in English | MEDLINE | ID: mdl-38244590

ABSTRACT

OBJECTIVE: To investigate the clinical characteristics of patients who presented with concomitant carpal tunnel syndrome (CTS) at the initial diagnosis with rheumatoid arthritis (RA). METHODS: We analyzed patients with newly diagnosed RA at a single institution between 2012 and 2021. Patient demographic and laboratory data, the 2010 ACR/EULAR classification criteria, and the duration from the initial visit to RA diagnosis were compared between RA patients with concomitant CTS (RA with CTS group) and those without CTS (RA without CTS group). RESULTS: The study included 235 patients (157 females), of which 11 patients (4.7%) presented with CTS at the initial diagnosis with RA. In the RA with CTS group, the age was significantly higher (P = .033), all patients were female, and anti-cyclic citrullinated peptide antibody (ACPA) was negative, and the duration to RA diagnosis was longer than in the RA without CTS group. Among all RA with CTS patients, ultrasonography showed power Doppler signal-positive tenosynovitis in the carpal tunnel, which is not usually detected in idiopathic CTS. CONCLUSIONS: Patients with concomitant CTS at the initial diagnosis with RA were characterized by old age, female sex, and negative ACPA. Patients with symptoms of CTS should undergo ultrasonography for early diagnosis of RA.

3.
J Orthop Sci ; 29(2): 660-667, 2024 Mar.
Article in English | MEDLINE | ID: mdl-36781308

ABSTRACT

BACKGROUND: MicroRNA is attracting attention as a therapeutic target for osteoarthritis. We focused on joint capsules and synovium in lumbar facet joint osteoarthritis. The purpose of this study was to identify microRNAs that are upregulated in lumbar facet joint capsules and synovium with osteoarthritis. METHODS: We included patients who underwent spinal fusion for degenerative lumbar spine diseases. We selected patients who had both early-stage and late-stage facet joint osteoarthritis in a single individual. We extracted joint capsule and synovium samples from these patients and isolated microRNAs. During the screening phase, we compared early-stage and late-stage osteoarthritis samples from the same individual. We identified microRNAs with >2-fold change in expression in 75% or more of patients with late-stage osteoarthritis using next generation sequencing. During the technical validation phase, the same samples were used for real-time polymerase chain reaction. We identified microRNAs with >2-fold change in expression in 62.5% or more of patients with late-stage osteoarthritis. RESULTS: Of 40 patients who underwent spinal fusion, we selected eight patients with both early-stage and late-stage facet joint osteoarthritis. During the screening phase, we identified eight upregulated microRNAs out of 2274 microRNAs in late-stage OA. In late-stage OA, two microRNAs (miR-133a-5p and miR-144-3p) were upregulated in seven patients and six microRNAs (miR-133a-3p, miR-133b, miR-206, miR-20a-5p, miR-301a-3p, and miR-32-5p) were upregulated in six patients. During the technical validation phase, we found significant upregulation of miR-144-3p expression in late-stage osteoarthritis compared with early-stage osteoarthritis. Expression of the other microRNAs was not significantly different according to the paired-t test. However, miR-133a-3p, miR-133b, and miR-206 were upregulated >2-fold in 62.5% or more of patients with late-stage osteoarthritis. CONCLUSIONS: Some of the microRNAs identified in this study might be involved in joint capsule degeneration or synovitis.


Subject(s)
MicroRNAs , Osteoarthritis , Zygapophyseal Joint , Humans , Zygapophyseal Joint/surgery , MicroRNAs/genetics , MicroRNAs/metabolism , Osteoarthritis/genetics , Osteoarthritis/surgery , Synovial Membrane , Up-Regulation
4.
Clin Case Rep ; 11(9): e7881, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37744618

ABSTRACT

A thin patient with a history of eating disorders developed basicervical femoral neck fracture bilaterally and simultaneously due to vitamin D deficiency osteomalacia. A careful evaluation in thin patients with thigh pain, including bone biopsy, is required to avoid overlooking osteomalacia.

5.
Langenbecks Arch Surg ; 408(1): 189, 2023 May 11.
Article in English | MEDLINE | ID: mdl-37166568

ABSTRACT

PURPOSE: Necrotizing soft-tissue infection (NSTI) is a surgical emergency associated with high mortality. This study primarily aimed to identify the factors associated with in-hospital mortality due to NSTI in the extremities at a single institution. Secondarily, we aimed to clarify the effectiveness of the optimal combination of hyperbaric oxygen therapy (HBOT) and surgery for NSTI treatment. STUDY DESIGN: Retrospective observational study. METHODS: This study included all patients newly diagnosed with NSTI in the extremity from 2003 to 2021 in our hospital. Factors associated with mortality, including patient's characteristics, duration from onset to hospitalization, NSTI type, and clinical data at the initial visit; acute disseminated intravascular coagulation (DIC), laboratory risk indicator for necrotizing fasciitis score, and sequential organ failure assessment score; treatment, initial surgery, surgery times, amputation, HBOT, combined surgery with HBOT, and clinical outcomes; amputation rate, mortality rate, and hospitalization duration were examined. RESULTS: A total of 37 cases were treated for NSTIs. The median age was 64 years (range: 22-86). Five cases (13.5%) died during hospitalization. Ten patients were diagnosed with DIC at the initial visit, of whom four died. HBOT combined with surgery was performed in 23 cases, and 16 cases underwent multiple surgeries. Factors associated with mortality included DIC (p = 0.015, 95% confidence interval [CI]: 0.015-0.633) and multiple surgeries combined with HBOT (p = 0.028, 95% CI: 1.302-95.418). CONCLUSION: This study demonstrates that DIC at the initial visit is associated with mortality in extremity NSTI. Additionally, HBOT might improve prognosis when combined with multiple surgeries.


Subject(s)
Fasciitis, Necrotizing , Soft Tissue Infections , Humans , Middle Aged , Soft Tissue Infections/surgery , Soft Tissue Infections/complications , Fasciitis, Necrotizing/surgery , Fasciitis, Necrotizing/complications , Prognosis , Hospitalization , Retrospective Studies , Risk Factors , Extremities
6.
Mod Rheumatol Case Rep ; 7(1): 24-27, 2023 01 03.
Article in English | MEDLINE | ID: mdl-35639881

ABSTRACT

We report a case of methicillin-resistant Staphylococcus aureus (MRSA) septic arthritis of the elbow detected by arthroscopic synovectomy in an 81-year-old woman with rheumatoid arthritis (RA) who was initially diagnosed with a rheumatoid arthritis flare-up. The patient was administered abatacept, an antirheumatic biological agent, as the synovial fluid culture was negative. Destruction of the joint progressed despite medication, and the patient underwent arthroscopic synovectomy. MRSA was detected in the culture of the synovium that was collected intraoperatively, and septic arthritis was diagnosed. The infection subsided with anti-MRSA antibiotics, but the patient continued to experience moderate pain and limited motion. In RA patients, it might be difficult to differentiate minor findings from infection. Arthroscopic synovectomy is one of the selectable procedures that should be actively considered when infection is suspected.


Subject(s)
Antirheumatic Agents , Arthritis, Infectious , Arthritis, Rheumatoid , Elbow Joint , Methicillin-Resistant Staphylococcus aureus , Female , Humans , Aged, 80 and over , Elbow Joint/surgery , Synovectomy , Arthroscopy/methods , Arthritis, Rheumatoid/complications , Arthritis, Rheumatoid/diagnosis , Arthritis, Rheumatoid/drug therapy , Arthritis, Infectious/diagnosis , Arthritis, Infectious/etiology , Antirheumatic Agents/therapeutic use
7.
Ann Rheum Dis ; 82(2): 262-271, 2023 Feb.
Article in English | MEDLINE | ID: mdl-36109140

ABSTRACT

OBJECTIVES: Osteoarthritis (OA) features ageing-related defects in cellular homeostasis mechanisms in articular cartilage. These defects are associated with suppression of forkhead box O (FoxO) transcription factors. FoxO1 or FoxO3 deficient mice show early onset OA while FoxO1 protects against oxidative stress in chondrocytes and promotes expression of autophagy genes and the essential joint lubricant proteoglycan 4 (PRG4). The objective of this study was to identify small molecules that can increase FoxO1 expression. METHODS: We constructed a reporter cell line with FoxO1 promoter sequences and performed high-throughput screening (HTS) of the Repurposing, Focused Rescue and Accelerated Medchem (ReFRAME) library . Hits from the HTS were validated and function was assessed in human chondrocytes, meniscus cells and synoviocytes and following administration to mice. The most promising hit, the histone deacetylase inhibitor (HDACI) panobinostat was tested in a murine OA model. RESULTS: Among the top hits were HDACI and testing in human chondrocytes, meniscus cells and synoviocytes showed that panobinostat was the most promising compound as it increased the expression of autophagy genes and PRG4 while suppressing the basal and IL-1ß induced expression of inflammatory mediators and extracellular matrix degrading enzymes. Intraperitoneal administration of panobinostat also suppressed the expression of mediators of OA pathogenesis induced by intra-articular injection of IL-1ß. In a murine OA model, panobinostat reduced the severity of histological changes in cartilage, synovium and subchondral bone and improved pain behaviours. CONCLUSION: Panobinostat has a clinically relevant activity profile and is a candidate for OA symptom and structure modification.


Subject(s)
Cartilage, Articular , Osteoarthritis , Humans , Mice , Animals , Forkhead Transcription Factors , Histone Deacetylase Inhibitors/metabolism , Panobinostat/metabolism , Osteoarthritis/pathology , Aging , Chondrocytes/metabolism , Cartilage, Articular/metabolism , Interleukin-1beta/metabolism
8.
Arthritis Res Ther ; 24(1): 235, 2022 10 18.
Article in English | MEDLINE | ID: mdl-36258202

ABSTRACT

BACKGROUND: Animal models of spontaneous osteoarthritis (OA) are sparse and not well characterized. The purpose of the present study is to examine OA-related changes and mechanisms in senescence-accelerated mouse prone 8 (SAMP8) that displays a phenotype of accelerated aging.  METHODS: Knees of male SAMP8 and SAM-resistant 1 (SAMR1) mice as control from 6 to 33 weeks of age were evaluated by histological grading systems for joint tissues (cartilage, meniscus, synovium, and subchondral bone), and µCT analysis. Gene expression patterns in articular cartilage were analyzed by real-time PCR. Immunohistochemistry was performed for OA-related factors, senescence markers, and apoptosis. RESULTS: Starting at 14 weeks of age, SAMP8 exhibited mild OA-like changes such as proteoglycan loss and cartilage fibrillation. From 18 to 33 weeks of age, SAMP8 progressed to partial or full-thickness defects with exposure of subchondral bone on the medial tibia and exhibited synovitis. Histological scoring indicated significantly more severe OA in SAMP8 compared with SAMR1 from 14 weeks [median (interquartile range): SAMR1: 0.89 (0.56-1.81) vs SAMP8: 1.78 (1.35-4.62)] to 33 weeks of age [SAMR1: 1.67 (1.61-1.04) vs SAMP8: 13.03 (12.26-13.57)]. Subchondral bone sclerosis in the medial tibia, bone mineral density (BMD) loss of femoral metaphysis, and meniscus degeneration occurred much earlier than the onset of cartilage degeneration in SAMP8 at 14 weeks of age. CONCLUSIONS: SAMP8 are a spontaneous OA model that is useful for investigating the pathogenesis of primary OA and evaluating therapeutic interventions.


Subject(s)
Cartilage, Articular , Osteoarthritis , Mice , Animals , Male , Disease Models, Animal , Osteoarthritis/genetics , Osteoarthritis/pathology , Cartilage, Articular/pathology , Tibia , Aging/metabolism , Proteoglycans
9.
Mod Rheumatol ; 32(2): 432-437, 2022 Feb 28.
Article in English | MEDLINE | ID: mdl-33853475

ABSTRACT

OBJECTIVE: To explore the trends in patient characteristics and implant survivorship (IS) for primary total knee arthroplasty (TKA) over the past three decades. METHODS: This retrospective study enrolled a total of 635 knees who underwent TKA from 1985 to 2014. They were divided into three groups: group A, 125 knees in 1985-1994; group B, 203 knees in 1995-2004; and group C, 307 knees A in 2005-2014. The patient characteristics and IS were compared. RESULTS: The mean age of patients undergoing TKA was getting older: 65.3 ± 9.7, 69.1 ± 10.0, and 74.6 ± 8.4 years, in groups A, B, and C, respectively (p = .001). The proportion of patients <60 years old with RA decreased (p < .001), whereas that of patients ≥ 80 years old with OA increased dramatically, it was 7.0%, 14.5%, and 32.0% in groups A, B, and C, respectively (p < .001). The IS free from infection was over 98% in all groups. Alternatively, the IS free from aseptic loosening become better, it was 83.7%, 95.2%, and 98.2% in groups A, B, and C, respectively (p = .014). CONCLUSIONS: From these trends, we can estimate that the number of patients undergoing TKA will further increase in the future in an aging society.


Subject(s)
Arthroplasty, Replacement, Knee , Knee Prosthesis , Aged, 80 and over , Humans , Knee Joint/surgery , Middle Aged , Prosthesis Failure , Reoperation , Retrospective Studies , Survivorship , Treatment Outcome
10.
Open Access Rheumatol ; 13: 103-109, 2021.
Article in English | MEDLINE | ID: mdl-33994814

ABSTRACT

PURPOSE: To investigate the incidence and clinical characteristics of rheumatoid arthritis (RA) presenting with shoulder monoarthritis. PATIENTS AND METHODS: Our study included 113 patients (77 females; mean age, 63.0 ± 13.1 years) whom we newly diagnosed with RA in 2012-2016. We investigated cases with onset from shoulder monoarthritis. Specifically, we examined physical findings, blood test results, radiographic findings, magnetic resonance imaging (MRI) findings, and duration from initial visit to diagnosis. RA was diagnosed based on the 2010 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) classification criteria. RESULTS: Overall, mean 2010 ACR/EULAR criteria score was 6.8 ± 1.8, and median duration to diagnosis was 3 days (interquartile range: 0-14). Two patients (1.8%) were identified as having RA with onset from shoulder monoarthritis. Both were late middle-aged women with MRI findings of rotator cuff tear and remarkable synovial proliferation. However, neither patient fulfilled the 2010 ACR/EULAR criteria. It took 85 and 98 days to make a definitive diagnosis, respectively. CONCLUSION: Early diagnosis is difficult when RA synovitis develops from shoulder monoarthritis, especially, in elderly patients who have a rotator cuff tear. In addition to MRI, culture-based and pathological examinations may be helpful for early diagnosis of RA.

11.
J Knee Surg ; 34(5): 546-551, 2021 Apr.
Article in English | MEDLINE | ID: mdl-31561256

ABSTRACT

The purpose of this study is to determine the influence of debridement in and around the bone tunnels on the prevalence of cyclops lesion (CL), after anterior cruciate ligament reconstruction (ACLR) with hamstring grafts. Our hypothesis was that bone tunnel debridement during ACLR would reduce the prevalence of CL. Methods for debridement in and around the bone tunnels after tunnel drilling were standardized and applied to 38 knees undergoing double-bundle ACLR between 2011 and 2014, Group A (debridement group). Group B (nondebridement group) included 56 knees in which bone tunnel debridement was not performed. Postoperative MRI was performed to evaluate the presence of CL and the following three criteria: (1) the intercondylar site of CL (grade 1-3), depending on its anterior extent along the femoral condyle; (2) posterior bowing of the ACL graft; and (3) the positional relationship between the frontmost fiber of ACL graft and Blumensaat's line. If CL caused loss of extension or pain or discomfort during knee extension, it was defined as symptomatic CL (SCL). CL was detected in 8 cases (21.1%) in Group A and 26 cases (46.4%) in Group B. The prevalence of CL was significantly lower in Group A than in Group B (p = 0.010), and the risk ratio of CL was 0.31 (95% confidence interval: 0.12-0.79). Furthermore, 10 patients in Group B had SCL, compared with none in Group A (p = 0.004). In Group A, the intercondylar site of CL was grade 1 in all cases, while in Group B, the CL grades were 1 (n = 17), 2 (n = 7), 3 (n = 2) (p = 0.008). There were no cases of posterior bowing of the ACL in Group A, but six cases in Group B (p = 0.023). Debridement in and around the bone tunnel is a simple and effective method of preventing CL and SCL after ACLR. The level of evidence for the study is 3.


Subject(s)
Anterior Cruciate Ligament Injuries/surgery , Anterior Cruciate Ligament Reconstruction/adverse effects , Anterior Cruciate Ligament Reconstruction/methods , Debridement/methods , Fibrosis/prevention & control , Hamstring Tendons/pathology , Adolescent , Adult , Anterior Cruciate Ligament/diagnostic imaging , Anterior Cruciate Ligament/surgery , Anterior Cruciate Ligament Injuries/diagnostic imaging , Child , Female , Femur/diagnostic imaging , Femur/surgery , Fibrosis/diagnostic imaging , Fibrosis/etiology , Hamstring Tendons/diagnostic imaging , Hamstring Tendons/transplantation , Humans , Incidence , Knee Joint/diagnostic imaging , Knee Joint/surgery , Magnetic Resonance Imaging , Male , Odds Ratio , Prospective Studies , Range of Motion, Articular , Tibia/diagnostic imaging , Tibia/surgery , Young Adult
12.
Sci Rep ; 10(1): 10077, 2020 06 22.
Article in English | MEDLINE | ID: mdl-32572077

ABSTRACT

To establish a histopathological scoring system for changes in subchondral bone in murine models of knee osteoarthritis (OA), three key parameters, subchondral bone plate (Subcho.BP) consisting of the combination of Subcho.BP.thickness (Subcho.BP.Th) and angiogenesis, bone volume (BV/TV) and osteophytes, were selected. The new grading system was tested in two mouse OA models, (1) senescence accelerated mouse (SAM)-prone 8 (SAMP8) as spontaneous OA model with SAM-resistant 1 (SAMR1) as control; (2) destabilization of the medial meniscus in C57BL/6 mice as surgical OA model. Results of the spontaneous OA model showed that Subcho.BP.Th was significantly wider, angiogenesis was greater, and BV/TV was higher in SAMP8 than SAMR1. Notably, subchondral bone score was dramatically higher in SAMP8 at 6 weeks than SAMR1, while OARSI cartilage scores became higher only at 14 weeks. In the surgical OA model, the results were similar to the spontaneous OA model, but osteophytes appeared earlier. There were strong correlations both in Subcho.BP.Th and BV/TV between this scoring system and µCT (r = 0.89, 0.84, respectively). Inter-rater reliabilities for each parameter using this system were more than 0.943. We conclude that this new histopathological scoring system is readily applicable for evaluating the early changes in aging and OA-affected murine subchondral bone.


Subject(s)
Aging/pathology , Bone and Bones/pathology , Osteoarthritis/pathology , Animals , Cartilage, Articular/pathology , Disease Models, Animal , Histological Techniques/methods , Histological Techniques/standards , Male , Menisci, Tibial/pathology , Mice , Mice, Inbred C57BL , Osteoarthritis, Knee/pathology , Osteophyte/pathology , Tibia/pathology
13.
J Shoulder Elbow Surg ; 28(5): 888-892, 2019 May.
Article in English | MEDLINE | ID: mdl-30799200

ABSTRACT

BACKGROUND: The pennation angle is an important architectural and functional feature of pennate muscles. The purpose of this study was to investigate the change in the pennation angle of the supraspinatus muscle after rotator cuff tear repair. MATERIALS AND METHODS: The study included 68 patients who underwent arthroscopic rotator cuff repair and magnetic resonance imaging. The size of the tear was measured under arthroscopic visualization. The pennation angle of the supraspinatus both preoperatively and postoperatively and the integrity of the repaired cuff were determined by magnetic resonance imaging. RESULTS: The preoperative pennation angle was significantly greater with enlargement of the tear size (P < .0001, analysis of variance). The retear rate was 29% in patients with medium tears and 59% in patients with large or massive tears. No retear was noted in patients with partial and small tears. The retear rate was 90.9% when the preoperative pennation angle was 20° or greater and was 12.3% when this angle was 19° or less, and the risk ratio for retear was 7.4 when this angle was 20° or greater. For repair-type tears, comparison between the preoperative and postoperative pennation angles showed a significant decrease in the mean value from 11.8° ± 3.7° to 9.9° ± 3.0° in the medium tear group (P = .007, paired t test) but no significant difference in the large or massive tear group (from 15.1° ± 7.0° to 13.3° ± 5.8°) (P = .33). For retear-type tears, no significance was found between groups. CONCLUSION: The preoperative pennation angle is directly correlated with the tear configuration and could be one of the prognostic factors for postoperative cuff integrity. To restore the pennation angle, primary repair is more appropriate in smaller rotator cuff tears than in medium-sized tears.


Subject(s)
Arthroscopy , Rotator Cuff Injuries/surgery , Rotator Cuff/pathology , Adult , Aged , Female , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Recurrence , Rotator Cuff/diagnostic imaging , Rotator Cuff/surgery , Treatment Outcome
14.
Bone Rep ; 9: 1-10, 2018 Dec.
Article in English | MEDLINE | ID: mdl-29992179

ABSTRACT

OBJECTIVES: Cathepsin K is expressed by osteoclasts and synovial fibroblasts and degrades key components of bone and cartilage. Inhibition of cathepsin K protease activity may be beneficial for the prevention of bone erosion and cartilage degradation in rheumatoid arthritis (RA). The collagen-induced arthritis (CIA) rat model is well established for studying the pathology and treatment of RA. We investigated the effect of ONO-KK1-300-01, a cathepsin K inhibitor (CKI), on arthritis and bone mineral density (BMD) in rats with CIA. METHODS: Seven-month-old female Sprague Dawley rats were divided into 5 groups: rats without CIA (CNT); CIA rats that underwent ovariectomy (OVX) and were treated with CKI; CIA rats that underwent OVX and were treated with vehicle (Veh); CIA rats that underwent sham surgery and were treated with CKI; and CIA rats that underwent sham surgery and were treated with Veh. CKI was orally administered at a dose of 15 mg/kg, thus initiating collagen sensitization, until death at 4 weeks. We evaluated hind paw thickness and the arthritis score every week until death. Radiographs of the resected left foot were obtained with a soft X-ray apparatus. Destruction of bone and cartilage was classified and scored as previously described by Engelhardt et al. BMD was measured by bone densitometry at the halfway point between the distal metaphysis and the diaphysis of the resected right femur. We also performed histomorphometry of the proximal left tibia, histological evaluation of arthritis, and a bone strength test. RESULTS: CKI administration significantly reduced hind paw thickness and the arthritis score, and prevented a decrease in BMD. The radiographic score was significantly lower in the CKI group than in the Veh group. In the histomorphometric analysis, bone-resorption parameters were significantly lower in the CKI groups than in the Veh groups. CKI significantly inhibited synovial proliferation in the CIA rats. In the bone strength test, the ultimate stress was significantly higher in the CKI groups than in the Veh groups. CONCLUSION: Our findings indicate that cathepsin K inhibitors may inhibit systemic and local bone loss, ameliorate arthritis, and attenuate the decrease of bone strength in an animal model of arthritis.

15.
Sci Transl Med ; 10(428)2018 02 14.
Article in English | MEDLINE | ID: mdl-29444976

ABSTRACT

Aging is a main risk factor for osteoarthritis (OA). FoxO transcription factors protect against cellular and organismal aging, and FoxO expression in cartilage is reduced with aging and in OA. To investigate the role of FoxO in cartilage, Col2Cre-FoxO1, 3, and 4 single knockout (KO) and triple KO mice (Col2Cre-TKO) were analyzed. Articular cartilage in Col2Cre-TKO and Col2Cre-FoxO1 KO mice was thicker than in control mice at 1 or 2 months of age. This was associated with increased proliferation of chondrocytes of Col2Cre-TKO mice in vivo and in vitro. OA-like changes developed in cartilage, synovium, and subchondral bone between 4 and 6 months of age in Col2Cre-TKO and Col2Cre-FoxO1 KO mice. Col2Cre-FoxO3 and FoxO4 KO mice showed no cartilage abnormalities until 18 months of age when Col2Cre-FoxO3 KO mice had more severe OA than control mice. Autophagy and antioxidant defense genes were reduced in Col2Cre-TKO mice. Deletion of FoxO1/3/4 in mature mice using Aggrecan(Acan)-CreERT2 (AcanCreERT-TKO) also led to spontaneous cartilage degradation and increased OA severity in a surgical model or treadmill running. The superficial zone of knee articular cartilage of Col2Cre-TKO and AcanCreERT-TKO mice exhibited reduced cell density and markedly decreased Prg4 In vitro, ectopic FoxO1 expression increased Prg4 and synergized with transforming growth factor-ß stimulation. In OA chondrocytes, overexpression of FoxO1 reduced inflammatory mediators and cartilage-degrading enzymes, increased protective genes, and antagonized interleukin-1ß effects. Our observations suggest that FoxO play a key role in postnatal cartilage development, maturation, and homeostasis and protect against OA-associated cartilage damage.


Subject(s)
Autophagy , Forkhead Transcription Factors/metabolism , Homeostasis , Osteoarthritis/pathology , Proteoglycans/metabolism , Animals , Animals, Newborn , Body Size , Bone and Bones/anatomy & histology , Cartilage, Articular/metabolism , Cartilage, Articular/pathology , Cell Proliferation , Cell Survival/genetics , Chondrocytes/metabolism , Gene Deletion , Gene Expression Regulation , Growth Plate/pathology , Homeostasis/genetics , Humans , Interleukin-1beta/metabolism , Mice, Knockout , Osteoarthritis/genetics , Proteoglycans/genetics , Transforming Growth Factor beta/metabolism
16.
BMC Musculoskelet Disord ; 16: 158, 2015 Jun 30.
Article in English | MEDLINE | ID: mdl-26123128

ABSTRACT

BACKGROUND: Mechanical loading of bones activates modeling and suppresses remodeling by promoting bone formation. Eldecalcitol is approved for the treatment of osteoporosis in Japan and is often used in patients undergoing exercise therapy. However, the effects of eldecalcitol on bone formation during mechanical loading are unknown. The aim of this study was to clarify the influence of eldecalcitol administration on bone response to mechanical loading using a four-point bending device. METHODS: Forty six-month-old female Wistar rats were randomized into four groups based on eldecalcitol dose (vehicle administration (VEH), low dose (ED-L), medium dose (ED-M), and high dose (ED-H)). Loads of 38 N were applied in vivo to the right tibia for 36 cycles at 2 Hz, by four-point bending, 3 days per week for 3 weeks. After calcein double-labeling, rats were sacrificed and tibial cross sections were prepared from the region with maximal bending at the central diaphysis. Histomorphometry was performed on the entire periosteal and endocortical surface of the tibiae, dividing the periosteum into lateral and medial surfaces. RESULTS: The effects of external loading on bone formation parameters were significant at all three surfaces. Bone formation parameters were highest in the ED-H group, and the effects of eldecalcitol on bone formation rate were significant at the endocortical surface. In addition, the interaction between loading and eldecalcitol dose significantly affected bone formation rate at the endocortical surface. CONCLUSIONS: Eldecalcitol enhanced the cortical bone response to mechanical loading and a synergistic effect was observed in a rat model.


Subject(s)
Osteogenesis/drug effects , Osteogenesis/physiology , Vitamin D/analogs & derivatives , Weight-Bearing/physiology , Animals , Bone Density/drug effects , Bone Density/physiology , Dose-Response Relationship, Drug , Female , Rats , Rats, Wistar , Vitamin D/pharmacology
17.
Bone ; 53(1): 277-83, 2013 Mar.
Article in English | MEDLINE | ID: mdl-23207800

ABSTRACT

The effects of BPs on bone formation during mechanical loading are still unknown. In this study, we evaluated the effect of minodronate on the cortical bone response to mechanical loading applied using a 4-point bending device. We used six-month old female Wistar rats and randomized into five groups (N=10/group): Vehicle administration (VEH), low dose minodronate administration (MIN-L, 0.01 mg/kg BW), middle dose minodronate administration (MIN-M, 0.1mg/kg BW), high-dose minodronate administration (MIN-H 1mg/kg BW), and very high-dose minodronate administration (MIN-VH, 10mg/kg BW). Minodronate or vehicle was administered orally using the feeding needle at a dosage 3 times/week for 3 weeks. Loads on the right tibia at 38 N for 36 cycles at 2 Hz were applied in vivo by 4-point bending on the same day for 3 weeks. After calcein double labeling the rats were sacrificed and tibial cross sections were prepared from the region with maximal bending at the central diaphysis. Histomorphometry was performed at the entire periosteal and endocortical surface of the tibiae, dividing the periosteum into lateral and medial surfaces. The formation surface was reduced significantly in MIN-H and MIN-VH groups at the medial surface, and in MIN-VH group at the endocortical surface of the loaded tibia (p<0.01 vs. VEH). The mineral appositional rate was reduced significantly in MIN-H and MIN-VH groups at the endocortical surface of the loaded tibia (p<0.01 vs. VEH). The bone formation rate was significantly reduced in MIN-H group at the medial surface, and in MIN-H and MIN-VH groups at the endocortical surface of the loaded tibia (p<0.01 vs. VEH). However, no significant differences were observed in any parameters between the VEH group and either the MIN-L or MIN-M groups for both the loaded and non-loaded tibiae. Based on previous preventive studies in OVX rats, the optimal dose of minodronate for the treatment of osteoporosis would be 0.03 mg/kg (0.21 mg/kg/week). Therefore, we used 0.1mg/kg of minodronate 3 times/week (0.30 mg/kg/week) that was close to 0.21 mg/kg/week. In conclusion, minodronate does not reduce the cortical bone response to mechanical loading at the optimal dose for the treatment of osteoporosis in rat model.


Subject(s)
Bone and Bones/drug effects , Methylhydrazines/pharmacology , Stress, Physiological , Animals , Body Weight/drug effects , Bone and Bones/physiology , Dose-Response Relationship, Drug , Female , Rats , Rats, Wistar
18.
Mod Rheumatol ; 20(5): 511-3, 2010 Oct.
Article in English | MEDLINE | ID: mdl-20461434

ABSTRACT

We report here a rare case of insufficiency fracture at the distal diaphysis of the radius in a patient with rheumatoid arthritis (RA) after synovectomy combined with the Sauvé-Kapandji procedure. A 71-year-old woman who had been diagnosed with RA had been consecutively treated with several disease-modifying antirheumatic drugs. She had undergone synovectomy of the right wrist combined with the Sauvé-Kapandji procedure, due to a tendon rupture, 2 years before the current presentation (first visit). Although she had not experienced any recent trauma, the wrist pain had increased after she had lifted up the bedding at the funeral of her friend about 1 month prior to her first visit. Radiographs of her right wrist taken at the second visit showed a fracture at the distal diaphysis of the radius at the level of the excision osteotomy of the distal ulna; however, no displacement of the distal fragment was observed. We immobilized her forearm in a long-arm cast. However, after 3 weeks of cast immobilization, a displacement of the distal fragment was observed. A manual reduction of the displacement was performed and the arm was again immobilized in a long-arm cast. However, 1 week later, a displaced distal fragment was again observed. Subsequently, she received an open reduction and internal fixation using a volar locking plate and screws with an autologous iliac crest bone graft. Bone union was completed by 8 months following the operation.


Subject(s)
Arthritis, Rheumatoid/surgery , Arthrodesis/adverse effects , Fractures, Stress/etiology , Postoperative Complications , Radius Fractures/etiology , Synovectomy , Tendons/surgery , Aged , Arthritis, Rheumatoid/complications , Bone Plates , Bone Screws , Bone Transplantation , Female , Fracture Fixation, Internal/methods , Fracture Healing , Fractures, Stress/surgery , Humans , Ilium/transplantation , Radius Fractures/surgery , Rupture , Tendon Injuries/surgery
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