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1.
Hip Int ; 33(2): 288-297, 2023 Mar.
Article in English | MEDLINE | ID: mdl-34102901

ABSTRACT

BACKGROUND: Worldwide, the majority of total hip arthroplasties (THAs) placed in patients <55 years are uncemented. However, little is known about the preferred method of fixation in revision hip arthroplasty in young patients. The aim of this study was to assess potential differences in the method of fixation used between primary and revision THA in young patients using data from the Dutch Arthroplasty Register. METHODS: All primary THA placed in patients younger than 55 years, registered in the LROI between 2007 and 2019 were included n = 28,516). Kaplan-Meier survival analyses were used to estimate the survival of primary THA by method of fixation. Additionally, survival of revision procedures that changed or did not change in method of fixation were estimated. McNemar's test was used to assess differences in the proportion of cemented and uncemented fixation between primary and revision THA. RESULTS: In all acetabular revisions, the use of cemented fixation increased statistically significant with 39% (95% CI, 34-45, p < 0.001) from 23% in primary THA to 62% in revision procedures. In all femoral revisions, the increase of cemented fixation was also statistically significant with 25% (95% CI, 19-31, p < 0.001), from 11% in primary THA to 36% in revision surgery. For both revised acetabular and femoral components, we found no statistically significant difference in the 5-year survival between revision procedures that changed or did not change in method of fixation. CONCLUSIONS: There was a significant change towards cemented fixation between primary and revision THA in young patients in the Netherlands, which was especially pronounced in acetabular revisions. No significant difference in short-term survival was found between revision procedures that changed or did not change in method of fixation. Long-term follow-up data are needed to evaluate the effect of this change in fixation method on the outcome of revision procedures in young patients.


Subject(s)
Arthroplasty, Replacement, Hip , Hip Prosthesis , Humans , Arthroplasty, Replacement, Hip/methods , Reoperation/methods , Netherlands/epidemiology , Prosthesis Failure , Risk Factors , Registries , Cohort Studies
2.
PLoS One ; 13(2): e0193487, 2018.
Article in English | MEDLINE | ID: mdl-29474431

ABSTRACT

INTRODUCTION: Untreated unilateral developmental dysplasia of the hip (DDH) results in asymmetry of gait and hip strength and may lead to early osteoarthritis, which is commonly treated with a total hip arthroplasty (THA). There is limited knowledge about the obtained symmetry of gait and hip strength after the THA. The objectives of this cross-sectional study were to: a) identify asymmetries between the operated and non-operated side in kinematics, kinetics and hip strength, b) analyze if increased walking speed changed the level of asymmetry in patients c) compare these results with those of healthy subjects. METHODS: Women (18-70 year) with unilateral DDH who had undergone unilateral THA were eligible for inclusion. Vicon gait analysis system was used to collect frontal and sagittal plane kinematic and kinetic parameters of the hip joint, pelvis and trunk during walking at comfortable walking speed and increased walking speed. Furthermore, hip abductor and extensor muscle strength was measured. RESULTS: Six patients and eight healthy subjects were included. In the patients, modest asymmetries in lower limb kinematics and kinetics were present during gait, but trunk lateral flexion asymmetry was evident. Patients' trunk lateral flexion also differed compared to healthy subjects. Walking speed did not significantly influence the level of asymmetry. The hip abduction strength asymmetry of 23% was not statistically significant, but the muscle strength of both sides were significantly weaker than those of healthy subjects. CONCLUSIONS: In patients with a DDH treated with an IBG THA modest asymmetries in gait kinematics and kinetics were present, with the exception of a substantial asymmetry of the trunk lateral flexion. Increased walking speed did not result in increased asymmetries in gait kinematics and kinetics. Hip muscle strength was symmetrical in patients, but significantly weaker than in healthy subjects. Trunk kinematics should be included as an outcome measure to assess the biomechanical benefits of the THA surgery after DDH.


Subject(s)
Arthroplasty, Replacement, Hip , Gait , Healthy Volunteers , Hip/physiopathology , Hip/surgery , Adolescent , Adult , Aged , Case-Control Studies , Cross-Sectional Studies , Female , Hip/pathology , Humans , Middle Aged , Phenotype , Young Adult
3.
Acta Orthop ; 89(1): 59-65, 2018 Feb.
Article in English | MEDLINE | ID: mdl-28931340

ABSTRACT

Background and purpose - Hip resurfacing (HR) is a treatment option promoted for hip arthritis in young and active patients. However, adverse reactions to metal are a concern and the search for non-metallic bearing options proceeds. We present the first clinical study performed in patients using a newly developed hydrophilic polymer-on-polymer hip resurfacing device. Patients and methods - After performing extensive hip simulator tests, biocompatibility testing and animal tests (ISO 14242-1,3; 10993-3,4,5,10,11), approval was obtained from the IRB committee to enroll 15 patients in the first clinical study in humans using this experimental polymer-on-polymer hip resurfacing device. All surgeries were done by 2 experienced hip resurfacing surgeons. Clinical scores and standard radiographs as well as routine MRIs were obtained at regular intervals. Results - The surgical technique proved feasible with successful implantation of the new device using PMMA cement fixation on both sides without complications. Postoperative imaging revealed a well-positioned and well-fixed polymer resurfacing hip arthroplasty in all 4 initial cases. All 4 patients were free of pain and had good function for the first 2 months. However, in all 4 cases early cup loosening occurred between 8 and 11 weeks after surgery, necessitating immediate closure of the study. All 4 patients had a reoperation and were revised to a conventional THA. Retrieval analyses confirmed early cup loosening at the implant-cement interface in all 4 cases. The femoral components remained well attached to the cement. The periprosthetic tissues showed only small amounts of polymeric wear debris and there was only a very mild inflammatory reaction to this. Interpretation - Early cup loosening mandated a premature arrest of this study. After additional laboratory testing this failure mode was found to be the result of a small, yet measurable contraction in the cup size after exposing these implants to biological fluid divalent ion fluctuations in vivo. Currently used preclinical tests had failed to detect this failure mechanism. Modification of the polymer is essential to overcome these problems and before the potential of a polymer-on-polymer resurfacing arthroplasty may be further evaluated in patients.


Subject(s)
Arthroplasty, Replacement, Hip/adverse effects , Hip Prosthesis/adverse effects , Prosthesis Failure/adverse effects , Hip Joint/diagnostic imaging , Hip Joint/surgery , Humans , Magnetic Resonance Imaging , Osteoarthritis, Hip/diagnostic imaging , Osteoarthritis, Hip/surgery , Polymers/therapeutic use , Radiography
4.
Acta Orthop ; 86(6): 678-83, 2015.
Article in English | MEDLINE | ID: mdl-26364842

ABSTRACT

BACKGROUND AND PURPOSE: Aseptic loosening and infection are 2 of the most common causes of revision of hip implants. Antibiotic prophylaxis reduces not only the rate of revision due to infection but also the rate of revision due to aseptic loosening. This suggests under-diagnosis of infections in patients with presumed aseptic loosening and indicates that current diagnostic tools are suboptimal. In a previous multicenter study on 176 patients undergoing revision of a total hip arthroplasty due to presumed aseptic loosening, optimized diagnostics revealed that 4-13% of the patients had a low-grade infection. These infections were not treated as such, and in the current follow-up study the effect on mid- to long-term implant survival was investigated. PATIENTS AND METHODS: Patients were sent a 2-part questionnaire. Part A requested information about possible re-revisions of their total hip arthroplasty. Part B consisted of 3 patient-related outcome measure questionnaires (EQ5D, Oxford hip score, and visual analog scale for pain). Additional information was retrieved from the medical records. The group of patients found to have a low-grade infection was compared to those with aseptic loosening. RESULTS: 173 of 176 patients from the original study were included. In the follow-up time between the revision surgery and the current study (mean 7.5 years), 31 patients had died. No statistically significant difference in the number of re-revisions was found between the infection group (2 out of 21) and the aseptic loosening group (13 out of 152); nor was there any significant difference in the time to re-revision. Quality of life, function, and pain were similar between the groups, but only 99 (57%) of the patients returned part B. INTERPRETATION: Under-diagnosis of low-grade infection in conjunction with presumed aseptic revision of total hip arthroplasty may not affect implant survival.


Subject(s)
Arthroplasty, Replacement, Hip/adverse effects , Prosthesis Failure , Prosthesis-Related Infections/diagnosis , Aged , Diagnostic Errors , Female , Humans , Male , Prospective Studies , Prosthesis Failure/etiology , Prosthesis-Related Infections/complications , Quality of Life , Surveys and Questionnaires , Time Factors
5.
Am J Phys Med Rehabil ; 93(6): 486-92, 2014 Jun.
Article in English | MEDLINE | ID: mdl-24508926

ABSTRACT

OBJECTIVE: The aim of the present study was to identify independent preoperative hip function characteristics sensitive for preoperative intervention that are predictive of an extended length of hospital stay (LOS) after primary total hip arthroplasty (THA). DESIGN: This is a longitudinal cohort study. A retrospective chart analysis was conducted on prospectively collected data of patients (158) who underwent unilateral primary elective cemented THA in a 4-yr period. The main outcome measure was LOS after primary THA. RESULTS: The median LOS was 6.0 days. The authors found an 18.5% increased chance of requiring an LOS of more than 6 days (odds ratio, 2.15; 95% confidence interval, 1.03-4.50) for the patients who needed to use a walking aid preoperatively and a 23.6% increased chance (odds ratio, 2.74; 95% confidence interval, 1.31-5.74) for the patients who had difficulties managing stairs. Sex, age, body mass index, comorbidity, and preoperative pain did not reach the level of significance in the multivariate analysis. CONCLUSIONS: Patients who are at risk for a longer stay in the hospital after THA can be identified preoperatively on simple physical function characteristics. These findings enable the identification of appropriate patients for preoperative training to improve functional recovery and decrease the LOS after primary THA.


Subject(s)
Arthroplasty, Replacement, Hip , Length of Stay/statistics & numerical data , Mobility Limitation , Preoperative Period , Aged , Arthroplasty, Replacement, Hip/rehabilitation , Canes , Cohort Studies , Crutches , Female , Health Status , Humans , Longitudinal Studies , Male , Multivariate Analysis , Retrospective Studies
6.
BMC Musculoskelet Disord ; 13: 44, 2012 Mar 24.
Article in English | MEDLINE | ID: mdl-22443362

ABSTRACT

BACKGROUND: Bone grafts from bone banks might be mixed with bisphosphonates to inhibit the osteoclastic response. This inhibition prevents the osteoclasts to resorb the allograft bone before new bone has been formed by the osteoblasts, which might prevent instability. Since bisphosphonates may not only inhibit osteoclasts, but also osteoblasts and thus bone formation, we studied different bisphosphonate concentrations combined with allograft bone. We investigated whether locally applied alendronate has an optimum dose with respect to bone resorption and formation. Further, we questioned whether the addition of demineralized bone matrix (DBM), would stimulate bone formation. Finally, we studied the effect of high levels of antibiotics on bone allograft healing, since mixing allograft bone with antibiotics might reduce the infection risk. METHODS: 25 goats received eight bone conduction chambers in the cortical bone of the proximal medial tibia. Five concentrations of alendronate (0, 0.5 mg/mL, 1 mg/mL, 2 mg/mL, and 10 mg/mL) were tested in combination with allograft bone and supplemented with cefazolin (200 µg/mL). Allograft not supplemented with alendronate and cefazolin served as control. In addition, allograft mixed with demineralized bone matrix, with and without alendronate, was tested. After 12 weeks, graft bone area and new bone area were determined with manual point counting. RESULTS: Graft resorption decreased significantly (p < 0.001) with increasing alendronate concentration. The area of new bone in the 1 mg/mL alendronate group was significantly (p = 0.002) higher when compared to the 10 mg/mL group. No differences could be observed between the group without alendronate, but with demineralized bone, and the control groups. CONCLUSIONS: A dose-response relationship for local application of alendronate has been shown in this study. Most new bone was present at 1 mg/mL alendronate. Local application of cefazolin had no effect on bone remodelling.


Subject(s)
Alendronate/administration & dosage , Anti-Bacterial Agents/administration & dosage , Bone Demineralization Technique , Bone Density Conservation Agents/administration & dosage , Bone Remodeling/drug effects , Bone Transplantation/methods , Cefazolin/administration & dosage , Sternum/transplantation , Tibia/drug effects , Animals , Bone Resorption/metabolism , Bone Resorption/physiopathology , Bone Resorption/prevention & control , Dose-Response Relationship, Drug , Female , Goats , Osteogenesis/drug effects , Tibia/metabolism , Tibia/pathology , Tibia/physiopathology , Time Factors
7.
Arthritis Rheum ; 64(5): 1477-87, 2012 May.
Article in English | MEDLINE | ID: mdl-22127564

ABSTRACT

OBJECTIVE: S100A8 and S100A9 are two Ca(2+) binding proteins classified as damage-associated molecular patterns or alarmins that are found in high amounts in the synovial fluid of osteoarthritis (OA) patients. The purpose of this study was to investigate whether S100A8 and/or S100A9 can interact with chondrocytes from OA patients to increase catabolic mediators. METHODS: Using immunohistochemistry, we stained for S100A8 and S100A9 protein, matrix metalloproteinases (MMPs), and a cartilage-breakdown epitope specific for MMPs (VDIPEN) in cartilage from OA donors. Isolated chondrocytes or explants from OA and non-OA donors were stimulated with S100A8 and/or S100A9. Messenger RNA and protein levels of MMPs, cytokines, and cartilage matrix molecules were determined with quantitative reverse transcription-polymerase chain reaction and Luminex techniques, respectively. For receptor blocking studies, specific inhibitors for Toll-like receptor 4 (TLR-4), receptor for advanced glycation end products (RAGE), and carboxylated glycans were used. RESULTS: In cartilage from OA patients, the expression of S100A8 and S100A9 protein close to chondrocytes was associated with proteoglycan depletion and expression of MMP-1, MMP-3, and VDIPEN. Stimulation of chondrocytes with S100A8 and S100A9 caused a strong up-regulation of catabolic markers (MMPs 1, 3, 9, and 13, interleukin-6 [IL-6], IL-8, and monocyte chemotactic protein 1) and down-regulation of anabolic markers (aggrecan and type II collagen), thereby favoring cartilage breakdown. Blocking TLR-4, but not carboxylated glycans or RAGE, inhibited the S100 effect. The catabolic S100 effect was significantly more pronounced in chondrocytes from OA patients as compared to those from non-OA patients, possibly due to higher TLR-4 expression. CONCLUSION: S100A8 and S100A9 have a catabolic effect on human chondrocytes that is TLR-4 dependent. OA chondrocytes are more sensitive than normal chondrocytes to S100 stimulation.


Subject(s)
Calgranulin A/metabolism , Calgranulin B/metabolism , Cartilage, Articular/metabolism , Chondrocytes/metabolism , Osteoarthritis/metabolism , Toll-Like Receptor 4/metabolism , Biomarkers/metabolism , Calgranulin A/administration & dosage , Calgranulin B/pharmacology , Cartilage Oligomeric Matrix Protein , Cartilage, Articular/drug effects , Cartilage, Articular/pathology , Cells, Cultured , Chondrocytes/drug effects , Chondrocytes/pathology , Cytokines/genetics , Cytokines/metabolism , Epitopes/metabolism , Extracellular Matrix Proteins/genetics , Extracellular Matrix Proteins/metabolism , Gene Expression , Glycoproteins/genetics , Glycoproteins/metabolism , Humans , Matrilin Proteins , Matrix Metalloproteinases/genetics , Matrix Metalloproteinases/metabolism , Oligopeptides/metabolism , Osteoarthritis/pathology , Peptide Fragments/metabolism , Receptor for Advanced Glycation End Products , Receptors, Immunologic/antagonists & inhibitors , Recombinant Proteins , Toll-Like Receptor 4/antagonists & inhibitors
9.
Phys Ther ; 91(4): 547-54, 2011 Apr.
Article in English | MEDLINE | ID: mdl-21350030

ABSTRACT

BACKGROUND: Little is known about the functional performance of patients after revision total hip arthroplasty with major acetabular bone impaction grafting. In general, these patients are assumed to perform worse due to a more advanced stage of periarticular tissue degeneration and multiple surgeries compared with patients with primary total hip arthroplasty (THA). OBJECTIVE: The main purpose of this study was to quantify the differences in performance of the sit-to-stand (STS) movement between patients with primary THA and patients with revision THA. DESIGN AND METHODS: In this study, the STS movement was analyzed kinematically (knee and hip angular extension velocity) and kinetically (loading symmetry ratio). Ten patients after primary THA and 10 patients after revision THA with acetabular bone impaction grafting were compared using these 3 rising parameters. RESULTS: The patients with revision THA performed the STS movement comparably to the patients with primary THA; there were no differences in knee and hip velocity or leg asymmetry during rising. LIMITATIONS: The study focused only on kinetic and kinematic aspects, and only patients who were satisfied with their THA were involved. CONCLUSIONS: This study showed that patients after a revision THA with acetabular bone impaction grafting and cement did not perform the STS movement differently, either kinematically or kinetically, compared with patients with a primary THA.


Subject(s)
Acetabulum/surgery , Arthroplasty, Replacement, Hip/methods , Hip Joint/physiopathology , Movement/physiology , Activities of Daily Living , Adult , Aged , Cementation , Female , Humans , Male , Middle Aged , Prospective Studies , Recovery of Function/physiology , Reoperation , Treatment Outcome
10.
Acta Orthop ; 81(6): 667-73, 2010 Dec.
Article in English | MEDLINE | ID: mdl-20919816

ABSTRACT

PURPOSE: We investigated the hypothesis that many total hip arthroplasty revisions that are classified as aseptic are in fact low-grade infections missed with routine diagnostics. METHODS: In 7 Dutch hospitals, 176 consecutive patients with the preoperative diagnosis of aseptic loosening of their total hip arthroplasty were enrolled. During surgery, between 14 and 20 tissue samples were obtained for culture, pathology, and broad-range 16S rRNA PCR with reverse line blot hybridization. Patients were classified as either not being infected, suspected of having infection, or infected according to strict, predefined criteria. Each patient had a follow-up visit after 1 year. RESULTS: 7 patients were classified as infected, 4 of whom were not identified by routine culture. 15 additional patients were suspected of having infection. 20 of these 22 patients received a cemented prosthesis, fixated with antibiotic-loaded bone cement. All 22 patients received prophylactic systemic antibiotics. 7 of them reported complaints one year after surgery, but only one showed signs of early loosening. However, additional surgery was not performed in any of the patients. INTERPRETATION: Although the proportions were not as high as previously reported in the literature, between 4% and 13% of patients with the preoperative diagnosis of aseptic loosening were infected. However, as thorough debridement was performed during surgery and prophylactic antibiotics were used, the diagnosis of infection did not have any obvious clinical consequences, as most patients performed well at the 1-year follow-up. Whether this observation has implications for long-term implant survival remains to be seen.


Subject(s)
Arthroplasty, Replacement, Hip/adverse effects , Prosthesis-Related Infections/etiology , Adult , Aged , Aged, 80 and over , Female , Follow-Up Studies , Hip Prosthesis/adverse effects , Humans , Incidence , Male , Middle Aged , Netherlands/epidemiology , Polymerase Chain Reaction , Prospective Studies , Prosthesis Failure , Prosthesis-Related Infections/epidemiology , Prosthesis-Related Infections/microbiology , Reoperation
11.
BMC Musculoskelet Disord ; 11: 96, 2010 May 25.
Article in English | MEDLINE | ID: mdl-20500808

ABSTRACT

BACKGROUND: Allograft bone used in joint replacement surgery can additionally serve as a carrier for antibiotics and serve as a prophylaxis against infections. However, in vitro dose-response curves for bone chips impregnated with different kinds of antibiotics are not available. In addition, while it would be desirable to add the antibiotics to allograft bone chips before these are stored in a bone bank, the effects of different storage temperatures on antibiotics are unknown. METHODS: Five different antibiotics (cefazolin, clindamycin, linezolid, oxacillin, vancomycin) were stored, both as pills and as solutions, at -80 degrees C, -20 degrees C, 4 degrees C, 20 degrees C and 37 degrees C; in addition, bone chips impregnated with cefazolin and vancomycin were stored at -80 degrees C and -20 degrees C. After 1 month, 6 months and 1 year, the activity of the antibiotics against Staphylococcus epidermidis was measured using an inoculated agar. The diameter of the S. epidermidis-free zone was taken as a measure of antibiotic activity. In a separate experiment, in vitro dose-response curves were established for bone chips impregnated with cefazolin and vancomycin solutions at five different concentrations. Finally, the maximum absorbed amounts of cefazolin and vancomycin were established by impregnating 1 g of bone chips with 5 ml of antibiotic solution. RESULTS: A decrease of the S. epidermidis-free zone was seen with oxacillin and cefazolin solutions stored at 37 degrees C for 1 month, with vancomycin stored at 37 degrees C for 6 months and with cefazolin and oxacillin solutions stored at 20 degrees C for 6 months. The activity of the other antibiotic solutions, pills and impregnated bone chips was not affected by storage. The in vitro dose-response curves show that the free-zone diameter increases logarithmically with antibiotic concentration. The absorbed antibiotic amount of one gram bone chips was determined. CONCLUSIONS: Storage of antibiotics in frozen form or storage of antibiotic pills at temperatures up to 37 degrees C for 12 months does not affect their activity. However, storage of antibiotic solutions at temperatures above 20 degrees C does affect the activity of some of the antibiotics investigated. The in vitro dose-response curve can be used to determine the optimal concentration(s) for local application. It provides the opportunity to determine the antibiotic content of bone chips, and thus the amount of antibiotics available locally after application.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Bone Transplantation/methods , Surgical Wound Infection/drug therapy , Transplantation, Homologous/methods , Acetamides/chemistry , Acetamides/therapeutic use , Anti-Bacterial Agents/chemistry , Antibiotic Prophylaxis , Bone Transplantation/adverse effects , Cefazolin/chemistry , Cefazolin/therapeutic use , Clindamycin/chemistry , Clindamycin/therapeutic use , Dose-Response Relationship, Drug , Drug Compounding , Drug Stability , Drug Storage , Humans , Linezolid , Microbial Sensitivity Tests , Oxacillin/chemistry , Oxacillin/therapeutic use , Oxazolidinones/chemistry , Oxazolidinones/therapeutic use , Prosthesis-Related Infections , Staphylococcus epidermidis/drug effects , Staphylococcus epidermidis/physiology , Surgical Wound Infection/prevention & control , Temperature , Transplantation, Homologous/adverse effects , Vancomycin/chemistry , Vancomycin/therapeutic use
12.
Arthritis Rheum ; 60(2): 501-12, 2009 Feb.
Article in English | MEDLINE | ID: mdl-19180479

ABSTRACT

OBJECTIVE: Wnt signaling pathway proteins are involved in embryonic development of cartilage and bone, and, interestingly, developmental processes appear to be recapitulated in osteoarthritic (OA) cartilage. The present study was undertaken to characterize the expression pattern of Wnt and Fz genes during experimental OA and to determine the function of selected genes in experimental and human OA. METHODS: Longitudinal expression analysis was performed in 2 models of OA. Levels of messenger RNA for genes from the Wnt/beta-catenin pathway were determined in synovium and cartilage, and the results were validated using immunohistochemistry. Effects of selected genes were assessed in vitro using recombinant protein, and in vivo by adenoviral overexpression. RESULTS: Wnt-induced signaling protein 1 (WISP-1) expression was strongly increased in the synovium and cartilage of mice with experimental OA. Wnt-16 and Wnt-2B were also markedly up-regulated during the course of disease. Interestingly, increased WISP-1 expression was also found in human OA cartilage and synovium. Stimulation of macrophages and chondrocytes with recombinant WISP-1 resulted in interleukin-1-independent induction of several matrix metalloproteinases (MMPs) and aggrecanase. Adenoviral overexpression of WISP-1 in murine knee joints induced MMP and aggrecanase expression and resulted in cartilage damage. CONCLUSION: This study included a comprehensive characterization of Wnt and Frizzled gene expression in experimental and human OA articular joint tissue. The data demonstrate, for the first time, that WISP-1 expression is a feature of experimental and human OA and that WISP-1 regulates chondrocyte and macrophage MMP and aggrecanase expression and is capable of inducing articular cartilage damage in models of OA.


Subject(s)
Arthritis, Experimental/metabolism , Intracellular Signaling Peptides and Proteins/metabolism , Oncogene Proteins/metabolism , Osteoarthritis, Hip/metabolism , Osteoarthritis, Knee/metabolism , Proto-Oncogene Proteins/metabolism , Animals , Arthritis, Experimental/genetics , CCN Intercellular Signaling Proteins , Cartilage, Articular/metabolism , Cartilage, Articular/pathology , Chondrocytes/drug effects , Chondrocytes/enzymology , Endopeptidases/biosynthesis , Gene Expression , Hindlimb/pathology , Humans , Immunohistochemistry , Intracellular Signaling Peptides and Proteins/genetics , Intracellular Signaling Peptides and Proteins/pharmacology , Joints/metabolism , Joints/pathology , Macrophages/drug effects , Macrophages/enzymology , Matrix Metalloproteinases/biosynthesis , Mice , Mice, Inbred C57BL , Oncogene Proteins/genetics , Osteoarthritis, Hip/genetics , Osteoarthritis, Knee/genetics , Proto-Oncogene Proteins/genetics , Proto-Oncogene Proteins/pharmacology , RNA, Messenger/metabolism , Recombinant Proteins/pharmacology , Signal Transduction/genetics , Synovial Membrane/metabolism
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