Takahashi N, Mundy G R, Kuehl T J, Roodman G D
VA Hospital, San Antonio, TX.
J Bone Miner Res. 1987 Aug;2(4):311-7. doi: 10.1002/jbmr.5650020408.
It is unknown if osteoclasts derived from animals at different developmental stages differ. To study this question, we used a long-term baboon marrow culture system in which osteoclast-like multinucleated cells (MNC) are formed. Fetal, newborn, or adult baboon marrow cultures were tested to determine if they differ in their responsiveness to osteotropic hormones. In fetal and newborn marrow cultures 1,25-dihydroxyvitamin D3 (1,25D3) at 10(-10) M significantly increased MNC formation with a maximal effect seen at 10(-9) M. Higher concentrations of 1,25D3 progressively decreased MNC formation. In contrast, in adult baboon marrow cultures, 10(-9) M 1,25D3 was required to significantly increase MNC formation, with a maximal affect at 10(-8) M 1,25D3. Calcitonin (25-200 ng/ml) inhibited MNC formation in fetal, newborn, or adult baboon marrow cultures treated with 1,25D3 in an identical manner. The effects of 1,25D3 on granulocyte-macrophage progenitor cells (CFU-GM), the probable precursors of MNC, were identical in fetal and adult baboon marrow cultures, with a significant inhibition of CFU-GM colony formation at 10(-8) M 1,25D3. These results suggest that 1) osteoclast precursors are more sensitive to some osteotropic hormones during the fetal and newborn periods, and 2) differences in the 1,25D3 sensitivity of osteoclast-like MNC formation in fetal, newborn, and adult baboon marrow cultures are not due to effects on early proliferating precursors but may result from effects of 1,25D3 on fusion of later precursors for MNC.
源自不同发育阶段动物的破骨细胞是否存在差异尚不清楚。为研究这个问题,我们使用了一种长期狒狒骨髓培养系统,该系统中会形成破骨细胞样多核细胞(MNC)。对胎儿、新生儿或成年狒狒的骨髓培养物进行测试,以确定它们对促骨激素的反应是否存在差异。在胎儿和新生儿骨髓培养物中,10^(-10) M的1,25 - 二羟基维生素D3(1,25D3)能显著增加MNC的形成,在10^(-9) M时达到最大效应。更高浓度的1,25D3会逐渐减少MNC的形成。相比之下,在成年狒狒骨髓培养物中,需要10^(-9) M的1,25D3才能显著增加MNC的形成,在10^(-8) M的1,25D3时达到最大效应。降钙素(25 - 200 ng/ml)以相同方式抑制了用1,25D3处理的胎儿、新生儿或成年狒狒骨髓培养物中MNC的形成。1,25D3对粒细胞 - 巨噬细胞祖细胞(CFU - GM)(MNC可能的前体细胞)的影响在胎儿和成年狒狒骨髓培养物中是相同的,在10^(-8) M的1,25D3时CFU - GM集落形成受到显著抑制。这些结果表明:1)破骨细胞前体在胎儿期和新生儿期对某些促骨激素更敏感;2)胎儿、新生儿和成年狒狒骨髓培养物中破骨细胞样MNC形成对1,25D3敏感性的差异不是由于对早期增殖前体细胞的影响,而是可能由1,25D3对MNC后期前体细胞融合的影响导致的。