Abstract
Early in the pathological process of osteoarthritis (OA), subchondral bone remodelling, which is related to altered osteoblast metabolism, takes place. In the present study, we explored in human OA subchondral bone whether chondroitin sulfate (CS), glucosamine sulfate (GS), or both together affect the major bone biomarkers, osteoprotegerin (OPG), receptor activator of nuclear factor-kappa B ligand (RANKL), and the pro-resorptive activity of OA osteoblasts. The effect of CS (200 μg/mL), GS (50 and 200 μg/mL), or both together on human OA subchondral bone osteoblasts, in the presence or absence of 1,25(OH)2D3 (vitamin D3) (50 nM), was determined on the bone biomarkers alkaline phosphatase and osteocalcin, on the expression (mRNA) and production (enzyme-linked immunosorbent assay) of bone remodelling factors OPG and RANKL, and on the pro-resorptive activity of these cells. For the latter experiments, human OA osteoblasts were incubated with differentiated peripheral blood mononuclear cells on a sub-micron synthetic calcium phosphate thin film. Data showed that CS and GS affected neither basal nor vitamin D3-induced alkaline phosphatase or osteocalcin release. Interestingly, OPG expression and production under basal conditions or vitamin D3 treatment were upregulated by CS and by both CS and GS incubated together. Under basal conditions, RANKL expression was significantly reduced by CS and by both drugs incubated together. Under vitamin D3, these drugs also showed a decrease in RANKL level, which, however, did not reach statistical significance. Importantly, under basal conditions, CS and both compounds combined significantly upregulated the expression ratio of OPG/RANKL. Vitamin D3 decreased this ratio, and GS further decreased it. Both drugs reduced the resorption activity, and statistical significance was reached for GS and when CS and GS were incubated together. Our data indicate that CS and GS do not overly affect cell integrity or bone biomarkers. Yet CS and both compounds together increase the expression ratio of OPG/RANKL, suggesting a positive effect on OA subchondral bone structural changes. This was confirmed by the decreased resorptive activity for the combination of CS and GS. These data are of major significance and may help to explain how these two drugs exert a positive effect on OA pathophysiology.
Highlights
Osteoarthritis (OA) is one of the most common joint disorders, affecting approximately 65% of individuals over 60 years of age, many of whom suffer from pain and functional disability, and resulting in a significant social and economic burden
Recent data showed that human OA subchondral bone osteoblasts could be discriminated into two groups according to low (L) or high (H) OA osteoblasts based on the level of prostaglandin E2
Human osteoarthritis subchondral bone osteoblast classification We previously showed that patients with OA can be discriminated into two groups classified according to L- or H-OA oste
Summary
Osteoarthritis (OA) is one of the most common joint disorders, affecting approximately 65% of individuals over 60 years of age, many of whom suffer from pain and functional disability, and resulting in a significant social and economic burden. Synovial membrane inflammation is believed to play an important role in the progression of joint tissue lesions; there is a general consensus that synovial inflammation in OA is not the primary cause of the disease but rather a secondary phenomenon related to multiple factors, including cartilage matrix degradation. Studies have demonstrated that, in OA, the subchondral bone is not an innocent bystander but is the site of several dynamic morphological changes that appear to be part of the disease process [2]. These changes are associated with a number of local abnormal biochemical pathways related to the altered osteoblast metabolism
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