To identify chondroprotective factors as potential disease-modifying osteoarthritis treatments using an unbiased, bottom-up proteomics approach.Paired equine cartilage explants and synovial membrane were collected postmortem from 4 horses with no history of lameness and grossly normal joints at necropsy.Six groups were established: cartilage, synoviocytes, and cartilage + synoviocytes (coculture), all with or without interleukin (IL)-1β. The catabolic effect of IL-1β was verified by glycosaminoglycan (GAG) released from cartilage into media by 1,9-dimethyl-methylene blue assay and cartilage toluidine blue histochemistry. Conditioned media from cocultures with or with IL-1β were submitted for bottom-up proteomic analysis. Synoviocyte gene expression was evaluated using reverse transcription-quantitative PCR (RT-qPCR) for proteins of interest identified in the proteomics scan.GAG content was retained in cartilage when in cocultures treated with IL-1β. Fourteen proteins of interest were selected from the proteomic analysis. From these 14 proteins, metalloproteinase inhibitor 3 precursor (TIMP3), tumor necrosis factor receptor superfamily member 11B (TNFRSF11B), insulin-like growth factor-binding protein 2 (IGFBP2), and alpha-2 macroglobulin (A2M) were selected for synoviocyte gene expression analysis by RT-qPCR. Gene expression of TIMP3 (P = .02) and TNFRSF11B (P = .04) were significantly increased in synoviocytes from cocultures treated with IL-1β compared to controls. Contrary to expectations based on protein expression, IGFBP2 gene expression (P = .04) was significantly decreased in IL-1β-stimulated coculture synoviocytes compared to control coculture synoviocytes. A2M gene expression in synoviocytes was not different between coculture groups.The secretome from synoviocytes could provide a milieu of bioactive factors to restore joint homeostasis in osteoarthritis.
PURPOSE: We report the outcome of a denned rehabilitation program for patients that have undergone surgical repair of cartilage lesions in arthritic knees and present outcome results over the first 12 years in 125 patients. METHODS: 125 arthritic patients with Outerbridge Grade IV lesions treated with an articular cartilage paste graft were followed for 2–12 years. Clinical success was measured by examination, MRI, radiographs, and validated pain, functioning, and activity questionnaires (IKDC, WOMAC, Tegner). Post-operative follow-up occurred at months 1, 3, and 6, and at years 1, 3, 5, 7, 9, 12, and 15. All patients followed a denned rehabilitation protocol including: pre-surgery evaluation and therapy and continued through post-operative therapy and exercise prescription in a staged program as follows: PROTECTIVE PHASE (wk1-4). This initial phase controls pain and inflammation that can results in guarding, loss of function, and scar formation. By phase end, the patient should have full extension and flexion similar to contralateral side, no persistent swelling, good patellar and scar mobilization, and minimal to no pain. FUNCTIONAL PHASE (wk4-8) A gradual progression is implemented from partial to full weight bearing. Weight bearing is customized to the location of the lesion or arthritis and transition assessed by gait analysis. ADVANCED FUNCTIONAL PHASE (wk8-12) Strengthening exercises allow for gradual return to functional and athletic goals. Low impact activities are indicated and include: road cycling, elliptical machines, treadmill, and cross-country skiing. By stage end, lateral movements are incorporated and geared towards individual sport goals RESULTS: A successful post-operative outcome was observed in 82% of subjects as denned through improved subjective scores from 2 to 12 years, p=0.001. CONCLUSIONS: We believe all patients with arthritis have abnormal gait and muscle patterns due to favoring, pain or swelling. Assessing these problems and working with operative patients in a pre to post-surgery comprehensive rehabilitation plan has been successfully used in conjunction with cartilage paste grafting. The durability of the paste grafting procedure permitted a rehabilitation program that, unlike total knee replacement, has returned patients to cutting and impact sports.
