Objective. To determine the phenotype of osteoblasts from the sclerotic zones of human osteoarthritic (OA) subchondral bone.Methods. Human osteoblasts were isolated from sclerotic or nonsclerotic areas of subchondral bone and cultured for 14 days in monolayer. The expression of 14 genes was investigated by real-time reverse transcriptionpolymerase chain reaction. The activities of alkaline phosphatase (AP) and transglutaminases (TGases) were quantified by enzymatic assays. C-terminal type I procollagen propeptide (CPI), interleukin-1␤ (IL-1␤), IL-6, IL-8, transforming growth factor ␤1 (TGF␤1), osteocalcin (OC), and osteopontin (OPN) were assayed in the culture medium by immunoassay.Results. Gene expression levels of matrix metalloproteinase 13, COL1A1 and COL1A2, OPN, tissuenonspecific AP, OC, vascular endothelial growth factor, ANKH, TGase 2, factor XIIIA, and dentin matrix protein 1 were significantly up-regulated in sclerotic osteoblasts compared with nonsclerotic osteoblasts. In contrast, parathyroid hormone receptor gene expression was depressed in sclerotic osteoblasts, but bone sialoprotein levels were unchanged. The activities of AP and TGases were increased in sclerotic osteoblasts, while matrix mineralization, revealed by alizarin red staining, was decreased. In parallel, protein synthesis of CPI, OC, OPN, IL-6, IL-8, and TGF␤1 was significantly higher in sclerotic osteoblasts than in nonsclerotic osteoblasts, while IL-1␤ production was similar in both groups.Conclusion. These findings contribute to a better understanding of the mechanisms involved in subchondral bone sclerosis and identify osteoblasts with an altered phenotype as a potential target for future OA therapies.Osteoarthritis (OA) is a common leading cause of disability in the elderly that is characterized by cartilage degradation, synovium and tendon inflammation, muscle weakness, osteophyte formation, and subchondral bone plate thickening (1). Although it is not yet clear whether it precedes (2-4) or occurs subsequently to cartilage damage (5-7), subchondral bone remodeling is an important feature in the pathophysiology of OA and is characterized by osteoid substance accumulation, decreased mineralization, and increased amounts of type I homotrimer (8). It is speculated that subchondral bone remodeling is linked to cartilage degradation, not only by modifying the mechanical properties of the subchondral bone (9) but also by releasing factors that may influence cartilage metabolism (10,11). Thus, the understanding of the mechanisms leading to bone sclerosis is of the utmost importance in the treatment of OA.Indeed, previous studies have demonstrated that some osteoblasts are phenotypically different and may produce increased levels of alkaline phosphatase (AP), osteocalcin (OC), transforming growth factor ␤1 (TGF␤1), insulin-like growth factor 1 (IGF-1), and urokinase plasminogen activator, while levels of IGF binding proteins 3, 4, and 5 are lower and plasminogen activator inhibitor 1 and interleukin-1␤ (IL-1␤) levels remain unchanged (12...

IntroductionThe objective of this study was to assess the number and magnitude of preoperative expectations and to correlate them with the degree of satisfaction expressed one year after Total Hip Arthroplasty (THA) or Total Knee Arthroplasty (TKA), in patients with severe and painful osteoarthritis (OA).Materials and MethodsPreoperative expectations (within 20 days prior to surgery) and postoperative satisfaction (one year after the intervention) were measured using the previously validated French version of the Hospital for Special Surgery Hip or Knee Replacement Expectations Survey. Postoperative satisfaction was measured using a specific scale, following the same methodology as that used for the assessment of expectations. Prediction of the satisfaction of the patients was performed using multivariate linear regression modelling.ResultsA total of 138 patients (80 THA and 58 TKA) completed the two parts of the study. The expectations score (mean ± SD) (range 0–100) was 72.58 ± 12.63 before THA and 69.10 ± 13.72 before TKA (p = 0.13). The number of expectations expressed was 14.34 ± 1.32 (out of a potential maximum of 18) before THA and 14.70 ± 2.29 (out of a potential maximum of 19) before TKA. After 1 year, THA generated a significantly higher degree of satisfaction compared to TKA (69.70 ± 14.46 v 60.44 ± 17.54, p<0.001) (range 0–100). The pre-operative expectations score was the single best positive predictor of the post-surgery satisfaction assessment both for TKA and THA.ConclusionPatients undergoing total joint arthroplasty for end-stage OA have a high level of expectations, before both THA and TKA. While both types of interventions significantly improve essential and non-essential activities, the rate of satisfaction is significantly greater post THA. Preoperative expectations are a major contributor to the final degree of satisfaction, one year after surgery. These results re-emphasize the need for an optimal preoperative interaction between health care providers and patients, to allow patients a chance to foresee a reasonable outcome after TJA.

Objective. Recent data have shown that abnormal subchondral bone remodeling plays an important role in osteoarthritis (OA) onset and progression, and it was suggested that abnormal mechanical pressure applied to the articulation was responsible for these metabolic changes. This study was undertaken to evaluate the effects of cyclic compression on osteoblasts from OA subchondral bone.Methods. Osteoblasts were isolated from sclerotic and nonsclerotic areas of human OA subchondral bone. After 28 days, the osteoblasts were surrounded by an abundant extracellular matrix and formed a resistant membrane, which was submitted to cyclic compression (1 MPa at 1 Hz) for 4 hours. Gene expression was evaluated by reverse transcription-polymerase chain reaction. Protein production in culture supernatants was quantified by enzyme-linked immunosorbent assay or visualized by immunohistochemistry.Results. Compression increased the expression of genes coding for interleukin-6 (IL-6), cyclooxygenase 2, RANKL, fibroblast growth factor 2, IL-8, matrix metalloproteinase 3 (MMP-3), MMP-9, and MMP-13 but reduced the expression of osteoprotegerin in osteoblasts in both sclerotic and nonsclerotic areas. Col␣1(I) and MMP-2 were not significantly affected by mechanical stimuli. Nonsclerotic osteoblasts were significantly more sensitive to compression than sclerotic ones, but after compression, differences in messenger RNA levels between nonsclerotic and sclerotic osteoblasts were largely reduced or even abolished. Under basal conditions, sclerotic osteoblasts expressed similar levels of ␣5, ␣v, ␤1, and ␤3 integrins and CD44 as nonsclerotic osteoblasts but 30% less connexin 43, an important mechanoreceptor.Conclusion. Genes involved in subchondral bone sclerosis are mechanosensitive. After compression, nonsclerotic and sclerotic osteoblasts expressed a similar phenotype, suggesting that compression could be responsible for the phenotype changes in OA subchondral osteoblasts.Osteoarthritis (OA) is a common cause of disability in the elderly, and is characterized by cartilage degradation, synovium and tendon inflammation, muscle weakness, osteophyte formation, and subchondral bone plate thickening (1). Although it is not yet clear if it precedes (2-4) or occurs subsequent to (5-7) cartilage damage, subchondral bone sclerosis is an important feature in OA pathophysiology, with local bone resorption and accumulation of weakly mineralized osteoid substance (8). Subchondral bone sclerosis is suspected to be linked to cartilage degradation, not only by modifying the mechanical properties of subchondral bone (9), but also by releasing biochemical factors that affect cartilage metabolism (10-12). Thus, understanding of the mechanisms leading to bone sclerosis would be an important factor in efforts to improve the treatment of OA. Previous studies have demonstrated that osteoblasts from sclerotic OA subchondral bone are phenotypically different from nonsclerotic osteoblasts (13-16). We have shown that osteoblasts from the thickened (sclerotic) subchond...

Hypertrophic differentiation of chondrocyte may promote angiogenesis. Our findings established the relation of BSP with OA chondrocyte hypertrophy and suggested that this factor could constitute a potential target to control cartilage neovascularisation in OA.

This study supports the implication of BSP in the pathology of OA and suggests that it could be a key mediator of the hypertrophic chondrocytes-induced angiogenesis. To control chondrocyte hypertrophic differentiation is promising in the treatment of OA.