Osteocalcin synthesis by human osteoblasts from normal and osteoarthritic bone after vitamin D3 stimulation
Osteocalcin synthesis by human osteoblasts from normal and osteoarthritic bone after vitamin D3 stimulation
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DOI：
10.1007/s10067-004-0928-1
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发表时间：
2004-12-01
影响因子：
3.4
通讯作者：
Melillo, N
中科院分区：
文献类型：
--
作者：
Cantatore, FP;Corrado, A;Melillo, N
成骨细胞代谢的改变参与了骨关节炎(OA)典型的软骨下骨改变的发病机制。骨钙素是成骨细胞合成的一种特殊的骨蛋白，可以被认为是成骨细胞代谢活性的标志。在这项研究中，我们将从健康人和骨关节炎患者分离的人成骨细胞产生的骨钙素与软骨损伤的程度相关联，在1，25(OH)(2)-维生素D-3，D-维生素D-3的活性代谢物刺激前后。我们从健康人的松质骨和骨关节炎患者的软骨下骨中分离出人成骨细胞，并将不同程度软骨损伤对应的成骨细胞视为不同的细胞群。我们测定了在基础条件下和维生素D-3刺激后，正常和骨关节炎成骨细胞在最大和最小软骨损伤区域的骨钙素产量。与正常成骨细胞相比，在基础条件下，骨关节炎成骨细胞的骨钙素产生显著增加，与关节最大和最小损伤区域相对应。最大损伤区和最小损伤区的成骨细胞之间没有差异。成骨细胞对维生素D-3刺激的反应似乎与关节损伤的程度成正比，因为在损伤最严重的成骨细胞中，维生素D-3诱导的骨钙素增加的比例高于损伤最轻的成骨细胞。因此，在维生素D-3刺激后，与最小损伤的成骨细胞相比，损伤最大的成骨细胞产生的骨钙素显著增加。这项研究证实了骨关节炎成骨细胞的异常行为，并表明来自同一受累关节不同区域的成骨细胞可能在代谢上存在差异，支持软骨下成骨细胞可能在骨关节炎的发病机制中发挥重要作用的假说。
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 D-3,D- the active metabolite of vitamin D-3. 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 D-3 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 D-3 stimulation appeared to be proportional to the degree of joint damage, as the vitamin D-3-induced increase in osteocalcin is proportionally greater in maximally damaged osteoblasts compared to minimally damaged ones. Thus, after vitamin D-3 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.