Lian J B, Marks S C
Department of Cell Biology, University of Massachusetts Medical School, Worcester 01655.
Endocrinology. 1990 Feb;126(2):955-62. doi: 10.1210/endo-126-2-955.
Osteocalcin, one of the vitamin K-dependent bone proteins, has recently been implicated in bone resorption. To explore this hypothesis, bone and serum osteocalcin were measured in three different osteopetrotic rat mutations characterized by reduced bone resorption. These three mutations (ia/ia, tl/tl, and op/op) exhibit heterogeneity with respect to osteoclast number and activity and response to being cured by bone marrow transplantation. Calvarial bone osteocalcin was present in normal amounts, but difficult to extract, in ia/ia rats that have increased numbers of inactive osteoclasts. Bone osteocalcin was greatly decreased in op/op (53-60% of control) and tl/tl (64-73% of control) osteopetrotic rats, in which osteoclasts are both reduced in number and inactive. These decreases in osteocalcin levels in bone coexist with elevated serum levels of osteocalcin in all three mutations. Since osteocalcin synthesis is known to be stimulated by 1,25(OH)2D3, the increase in serum osteocalcin may be a reflection of the elevated blood levels of 1,25(OH)2D3 known to occur in each of these mutations. These findings indicate that the composition of osteopetrotic bone is abnormal with respect to osteocalcin in the two rat osteopetrotic mutations showing decreased osteoclast numbers. Considered together with the emerging evidence that the extracellular matrix in many developing tissues plays a role in cell recruitment and differentiation, these data suggest that osteocalcin abnormalities may be a contributing factor to the spectrum of osteoclast aberrations in osteopetrosis.
骨钙素是维生素K依赖的骨蛋白之一，最近被认为与骨吸收有关。为了探究这一假说，我们在三种不同的骨质石化大鼠突变体中测量了骨和血清中的骨钙素，这些突变体的特征是骨吸收减少。这三种突变体（ia/ia、tl/tl和op/op）在破骨细胞数量、活性以及对骨髓移植治愈的反应方面表现出异质性。在破骨细胞数量增加但无活性的ia/ia大鼠中，颅骨骨钙素含量正常，但难以提取。在op/op（为对照的53 - 60%）和tl/tl（为对照的64 - 73%）骨质石化大鼠中，骨钙素大幅降低，这些大鼠的破骨细胞数量减少且无活性。在所有这三种突变体中，骨钙素水平在骨中的降低与血清骨钙素水平的升高并存。由于已知骨钙素的合成受1,25(OH)2D3刺激，血清骨钙素的增加可能反映了这些突变体中均出现的1,25(OH)2D3血水平升高。这些发现表明，在两种破骨细胞数量减少的大鼠骨质石化突变体中，骨质石化骨的组成在骨钙素方面是异常的。结合越来越多的证据表明许多发育中的组织中的细胞外基质在细胞募集和分化中起作用，这些数据表明骨钙素异常可能是骨质石化中破骨细胞异常谱的一个促成因素。
