Regulation of subchondral bone osteoblast metabolism by cyclic compression

Abstract

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...

Identification of shoulder osteoarthritis biomarkers: comparison between shoulders with and without osteoarthritis

“…Increased Cx43 in osteoarthritic joints has biological plausibility considering that increased mechanical load can lead to both the degradation of joints and an increase in Cx43. 15,42 This might support treatment protocols aimed at reducing stress at the glenohumeral joint.…”

Biomechanics and pathomechanisms of osteoarthritis

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Recent advances in the understanding of molecular mechanisms of cartilage degeneration, synovitis and subchondral bone changes in osteoarthritis

“…Further, under basal conditions, OA osteoblasts produce more insulinlike growth factor-1 and urokinase than normal cells. It has also been reported that subchondral bone explants from OA patients produce more IL-6, IL-8, and MMP-13 (154) as well as osteopontin, osteocalcin, TGF-β1, type I collagen, IL-6, IL-8, and high levels of alkaline phosphatase (ALP) but downregulated osteoprotegerin (OPG) gene expression and protein production (155)(156)(157). IL-6 and PGE2 stimulate receptor activator of nuclear factor Kappa-B-/Ligand (RANKL) and inhibit OPG production by osteoblasts and thus increase osteoclast differentiation and activation via their effect on the RANK/RANKL/OPG system (158,159).…”