Cantatore Francesco Paolo, Corrado Addolorata, Grano Maria, Quarta Laura, Colucci Silvia, Melillo Nadia
D'Avanzo Hospital, Chair of Rheumatology, University of Foggia, Via Ascoli, 71100 Foggia, Italy.
Clin Rheumatol. 2004 Dec;23(6):490-5. doi: 10.1007/s10067-004-0928-1.
Alterations in osteoblast metabolism are involved in the pathogenesis of typical subchondral bone changes in osteoarthritis (OA). Osteocalcin is a specific bone protein, synthesised by the osteoblasts, which can be considered a marker of metabolic activity of these cells. In this study we correlated osteocalcin production from human osteoblasts isolated from healthy and osteoarthritic subjects to the degree of cartilage damage, before and after stimulation with 1,25(OH)2-vitamin D3, the active metabolite of vitamin D3. We isolated human osteoblasts from cancellous bone of healthy subjects and from subchondral bone of osteoarthritic subjects and considered the osteoblasts corresponding to different degrees of cartilage damage as different cell populations. We determined the osteocalcin production in normal and osteoarthritic osteoblasts from maximal and minimal cartilage damage areas both under basal conditions and after vitamin D3 stimulation. Compared to normal osteoblasts, under basal conditions osteocalcin production is significantly greater in osteoarthritic osteoblasts, corresponding both to maximal and minimal damage joint areas. No differences were observed between osteoblasts from maximal and minimal damage areas. The response of osteoblasts to vitamin D3 stimulation appeared to be proportional to the degree of joint damage, as the vitamin D3-induced increase in osteocalcin is proportionally greater in maximally damaged osteoblasts compared to minimally damaged ones. Thus, after vitamin D3 stimulation, a significant increase in osteocalcin production by maximally damaged osteoblasts compared to the minimally damaged ones was observed. This study confirms abnormal osteoarthritic osteoblast behaviour and indicates that osteoblasts from different areas of the same affected joint may be metabolically different, supporting the hypothesis that subchondral osteoblasts may play an essential role in the pathogenesis of OA.
成骨细胞代谢改变参与骨关节炎（OA）典型软骨下骨变化的发病机制。骨钙素是一种由成骨细胞合成的特异性骨蛋白，可被视为这些细胞代谢活性的标志物。在本研究中，我们将从健康和骨关节炎受试者分离的人成骨细胞产生的骨钙素与软骨损伤程度相关联，观察在1,25(OH)2 - 维生素D3（维生素D3的活性代谢产物）刺激前后的情况。我们从健康受试者的松质骨和骨关节炎受试者的软骨下骨中分离出人成骨细胞，并将对应不同程度软骨损伤的成骨细胞视为不同的细胞群体。我们测定了来自最大和最小软骨损伤区域的正常和骨关节炎成骨细胞在基础条件下以及维生素D3刺激后的骨钙素产生情况。与正常成骨细胞相比，在基础条件下，骨关节炎成骨细胞（对应最大和最小损伤关节区域）的骨钙素产生显著更高。最大和最小损伤区域的成骨细胞之间未观察到差异。成骨细胞对维生素D3刺激的反应似乎与关节损伤程度成正比，因为与最小损伤的成骨细胞相比，最大损伤的成骨细胞中维生素D3诱导的骨钙素增加比例更大。因此，在维生素D3刺激后，观察到最大损伤的成骨细胞与最小损伤的成骨细胞相比，骨钙素产生有显著增加。本研究证实了骨关节炎成骨细胞的异常行为，并表明同一受累关节不同区域的成骨细胞在代谢上可能不同，支持软骨下成骨细胞可能在OA发病机制中起重要作用的假说。
