Martínez M E, Medina S, Sánchez M, Del Campo M T, Esbrit P, Rodrigo A, Martínez P, Sánchez-Cabezudo M J, Moreno I, Garcés M V, Munuera L
Biochemical Division, Hospital La Paz, Madrid, Spain.
Bone. 1999 Mar;24(3):203-9. doi: 10.1016/s8756-3282(98)00181-1.
Age-related bone loss may be a consequence of a lack of osteoblastic formation and/or function. In vitro, the osteoblastic response to 1,25(OH)2D3, an important regulator of osteoblastic function, appears to depend on the stage of osteoblastic maturation. In this study, we examined the response to 1,25(OH)2D3 of C-terminal type I procollagen (PICP), alkaline phosphatase (ALP), and osteocalcin (OC) secretion in primary cultures of osteoblastic cells from human trabecular bone (hOB). Forty-four bone samples were obtained from subjects undergoing knee arthroplastia, 20 aged 50-70 (64 +/- 5), and 24 >70 (73 +/- 2) years. Another 33 bone samples were obtained from subjects undergoing hip arthroplastia, 21 were aged 50-70 (64 +/- 4) and 12 >70 (75 +/- 5) years. Pooling knee and hip hOB cell cultures, we found that PICP secretion decreased after 1,25(OH)2D3 in hOB cells from the older group (>70 years). Treatment with 1,25(OH)2D3 increased ALP secretion in these cells only in the younger group (50-70 years), whereas it increased OC secretion in hOB cells in both age groups. By pooling hOB cell cultures from both age groups we found that knee hOB cells increased OC secretion, and decreased PICP secretion, after 1,25(OH)2D3. This metabolite also increased OC secretion in hip hOB cells. Considering the influence of donor age at the same skeletal site, 1,25(OH)2D3 was found to stimulate ALP secretion only in knee hOB cells in the younger group. In contrast, this metabolite decreased ALP secretion in hip hOB cells in the older group. PICP secretion decreased after 1,25(OH)2D3 only in hOB cells in the older group, at both skeletal sites. In age-matched cultures, OC secretion was lower in hip hOB cells compared with those from the knee in the older group, but was similar in these cell cultures from both skeletal sites in the younger group. OC secretion after 1,25(OH)2D3 stimulation did not show age differences in knee hOB cells, but was lower in hip hOB in the older group. In summary, our results demonstrate that the response of various osteoblastic markers to 1,25(OH)2D3 in primary cultures of hOB cells depends on the donor age and skeletal site of origin.
与年龄相关的骨质流失可能是成骨细胞形成和/或功能不足的结果。在体外，成骨细胞对1,25(OH)2D3（成骨细胞功能的重要调节因子）的反应似乎取决于成骨细胞成熟的阶段。在本研究中，我们检测了来自人小梁骨（hOB）的成骨细胞原代培养物中I型前胶原C端（PICP）、碱性磷酸酶（ALP）和骨钙素（OC）分泌对1,25(OH)2D3的反应。从接受膝关节置换术的受试者中获取了44块骨样本，其中20名年龄在50 - 70岁（64±5岁），24名年龄大于70岁（73±2岁）。另外从接受髋关节置换术的受试者中获取了33块骨样本，其中21名年龄在50 - 70岁（64±4岁），12名年龄大于70岁（75±5岁）。将膝关节和髋关节的hOB细胞培养物合并后，我们发现老年组（>70岁）hOB细胞在1,25(OH)2D3作用后PICP分泌减少。1,25(OH)2D3处理仅在年轻组（50 - 70岁）的这些细胞中增加了ALP分泌，而在两个年龄组的hOB细胞中均增加了OC分泌。通过合并两个年龄组的hOB细胞培养物，我们发现膝关节hOB细胞在1,25(OH)2D3作用后增加了OC分泌并减少了PICP分泌。这种代谢产物在髋关节hOB细胞中也增加了OC分泌。考虑到同一骨骼部位供体年龄的影响，发现1,25(OH)2D3仅在年轻组的膝关节hOB细胞中刺激ALP分泌。相反，这种代谢产物在老年组的髋关节hOB细胞中减少了ALP分泌。在两个骨骼部位，仅老年组的hOB细胞在1,25(OH)2D3作用后PICP分泌减少。在年龄匹配的培养物中，老年组髋关节hOB细胞的OC分泌低于膝关节hOB细胞，但在年轻组中，来自这两个骨骼部位的这些细胞培养物中的OC分泌相似。1,25(OH)2D3刺激后，膝关节hOB细胞的OC分泌没有显示出年龄差异，但老年组髋关节hOB细胞的OC分泌较低。总之，我们的结果表明，hOB细胞原代培养物中各种成骨细胞标志物对1,25(OH)2D3的反应取决于供体年龄和起源的骨骼部位。
