ALKALINE-PHOSPHATASE LEVELS AND OSTEOPROGENITOR CELL NUMBERS SUGGEST BONE-FORMATION MAY CONTRIBUTE TO PEAK BONE-DENSITY DIFFERENCES BETWEEN2 INBRED STRAINS OF MICE

Previous studies have shown that C3H/HeJ (C3H) mice have higher peak b one density than C57BL/6J (B6) mice, at least in part because of diffe rences in rates of bone resorption. The current studies were intended to examine the alternative, additional hypothesis that the greater bon e density in C3H mice might also be a consequence of increased bone fo rmation, 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 marr ow stromal cell cultures, We found that C3H mice had higher serum leve ls of ALP activity than B6 mice at 6 (118 vs, 100 U/L, p < 0.03) and 3 2 weeks of age (22.2 vs, 17.2 U/L, p < 0.001), Tibiae from C3H mice al so 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-derive d cells from explants of 7.5-week-old C3H calvariae and femora (8.2 ti mes more, p < 0.02, and 4.6 times more, p < 0.001, respectively), Mono layer cell cultures prepared by collagenase digestion of calvariae fro m newborn and 6-week-old mice also showed similar strain-dependent dif ferences in ALP-specific activity (p < 0.001 for each), Our studies al so showed more ALP-positive CFU in bone marrow stromal cell cultures f rom 8-week-old C3H mice, compared with B6 mice (72.3 vs, 26.1 ALP-posi tive CFU/culture dish, p < 0.001), A similar result was seen for ALP-p ositive CFU production at 6 and 14 weeks of age, and the difference wa s greatest for the CFU that contained the greatest numbers of ALP-posi tive cells, Because skeletal ALP activity is a product of osteoblasts and has been shown to correlate with rates of bone formation, and beca use the number of ALP-positive CFU is believed to reflect the number o f osteoprogenitor cells, the current data are consistent with the gene ral 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 formati on. (C) 1998 by Elsevier Science Inc. All rights reserved.