Alkaline phosphatase levels and osteoprogenitor cell numbers suggest bone formation may contribute to peak bone density differences between two inbred strains of mice
Alkaline phosphatase levels and osteoprogenitor cell numbers suggest bone formation may contribute to peak bone density differences between two inbred strains of mice
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DOI：
10.1016/s8756-3282(97)00268-8
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发表时间：
1998-03-01
期刊：
影响因子：
4.1
通讯作者：
Baylink, DJ
中科院分区：
文献类型：
--
作者：
Dimai, HP;Linkhart, TA;Baylink, DJ
先前的研究表明，C3 H/HeJ（C3 H）小鼠的峰值骨密度高于C57 BL/6 J（B6）小鼠，至少部分原因是骨吸收速率的差异。本研究旨在验证另一种假设，即C3 H小鼠骨密度的增加也可能是骨形成增加的结果。为此，我们测定了这些近交系小鼠骨形成和成骨细胞数量的两个假定的间接指标：血清、骨和骨细胞中的碱性磷酸酶（ALP）活性;结果发现，C_3H小鼠血清ALP活性高于B_6小鼠，而B_6小鼠血清ALP活性高于C_3H小鼠。（118 vs，100 U/L，p < 0.03）和32周龄（22.2vs，17.2U/L，p < 0.001），在6 ℃时，来自C3 H小鼠的肽也比来自B6小鼠的肽含有更高水平的ALP活性（417对254 mU/mg蛋白，p < 0.02）和14周龄（132 vs，79 mU/mg蛋白，p < 0.001），来自7.5周龄C3 H颅骨和股骨外植体的骨源性细胞单层培养物也是如此。（分别为8.2倍，p < 0.02和4.6倍，p < 0.001），通过胶原酶消化新生小鼠和6周龄小鼠颅骨制备的单层细胞培养物也显示出类似的ALP特异性活性的品系依赖性差异我们的研究还表明，与B6小鼠相比，8周龄C3 H小鼠的骨髓基质细胞培养物中ALP阳性CFU更多（72.3 vs，26.1 ALP阳性CFU/培养皿，p < 0.001），6周龄和14周龄时ALP阳性CFU产生的结果相似，并且包含最多数量ALP的CFU差异最大阳性细胞，因为骨骼ALP活性是成骨细胞的产物，并且已经显示与骨形成速率相关，并且因为ALP阳性CFU的数量被认为反映了骨祖细胞的数量，所以目前的数据与一般假设一致，即由于成骨细胞数量的差异，C3 H小鼠的骨形成可能大于B6小鼠，我们的数据进一步表明，由于骨吸收减少和骨形成增加的结合，C3 H小鼠的峰值骨密度可能高于B6小鼠。(C)1998年，Elsevier Science Inc. All rights reserved.
Previous studies have shown that C3H/HeJ (C3H) mice have higher peak bone density than C57BL/6J (B6) mice, at least in part because of differences in rates of bone resorption. The current studies were intended to examine the alternative, additional hypothesis that the greater bone density in C3H mice might also be a consequence of increased bone formation, To that end, we measured two presumptive, indirect indices of bone formation and osteoblast number in these inbred strains of mice: alkaline phosphatase (ALP) activity in serum, bones, and bone cells; and the number of ALP-positive colony-forming units (CFU) in bone marrow stromal cell cultures, We found that C3H mice had higher serum levels of ALP activity than B6 mice at 6 (118 vs, 100 U/L, p < 0.03) and 32 weeks of age (22.2 vs, 17.2 U/L, p < 0.001), Tibiae from C3H mice also contained higher levels of ALP activity than tibiae from B6 mice at 6 (417 vs, 254 mU/mg protein, p < 0.02) and 14 weeks of age (132 vs, 79 mU/mg protein, p < 0.001), as did monolayer cultures of bone-derived cells from explants of 7.5-week-old C3H calvariae and femora (8.2 times more, p < 0.02, and 4.6 times more, p < 0.001, respectively), Monolayer cell cultures prepared by collagenase digestion of calvariae from newborn and 6-week-old mice also showed similar strain-dependent differences in ALP-specific activity (p < 0.001 for each), Our studies also showed more ALP-positive CFU in bone marrow stromal cell cultures from 8-week-old C3H mice, compared with B6 mice (72.3 vs, 26.1 ALP-positive CFU/culture dish, p < 0.001), A similar result was seen for ALP-positive CFU production at 6 and 14 weeks of age, and the difference was greatest for the CFU that contained the greatest numbers of ALP-positive cells, Because skeletal ALP activity is a product of osteoblasts and has been shown to correlate with rates of bone formation, and because the number of ALP-positive CFU is believed to reflect the number of osteoprogenitor cells, the current data are consistent with the general hypothesis that bone formation may be greater in C3H than B6 mice because of a difference in osteoblast number, Our data further suggest that peak bone density may be greater in C3H mice than B6 mice due to a combination of decreased bone resorption and increased bone formation. (C) 1998 by Elsevier Science Inc. All rights reserved.