Xu T, Bianco P, Fisher L W, Longenecker G, Smith E, Goldstein S, Bonadio J, Boskey A, Heegaard A M, Sommer B, Satomura K, Dominguez P, Zhao C, Kulkarni A B, Robey P G, Young M F
Craniofacial and Skeletal Diseases Branch, National Institute of Dental Research, National Institutes of Health, Bethesda, Maryland 20892, USA.
Nat Genet. 1998 Sep;20(1):78-82. doi: 10.1038/1746.
The resilience and strength of bone is due to the orderly mineralization of a specialized extracellular matrix (ECM) composed of type I collagen (90%) and a host of non-collagenous proteins that are, in general, also found in other tissues. Biglycan (encoded by the gene Bgn) is an ECM proteoglycan that is enriched in bone and other non-skeletal connective tissues. In vitro studies indicate that Bgn may function in connective tissue metabolism by binding to collagen fibrils and TGF-beta (refs 5,6), and may promote neuronal survival. To study the role of Bgn in vivo, we generated Bgn-deficient mice. Although apparently normal at birth, these mice display a phenotype characterized by a reduced growth rate and decreased bone mass due to the absence of Bgn. To our knowledge, this is the first report in which deficiency of a non-collagenous ECM protein leads to a skeletal phenotype that is marked by low bone mass that becomes more obvious with age. These mice may serve as an animal model to study the role of ECM proteins in osteoporosis.
骨骼的韧性和强度归因于一种特殊细胞外基质（ECM）的有序矿化，该基质由I型胶原蛋白（90%）和许多非胶原蛋白组成，这些非胶原蛋白通常也存在于其他组织中。双糖链蛋白聚糖（由基因Bgn编码）是一种ECM蛋白聚糖，在骨骼和其他非骨骼结缔组织中含量丰富。体外研究表明，双糖链蛋白聚糖可能通过与胶原纤维和转化生长因子-β结合而在结缔组织代谢中发挥作用（参考文献5、6），并且可能促进神经元存活。为了研究双糖链蛋白聚糖在体内的作用，我们培育出了双糖链蛋白聚糖缺陷型小鼠。这些小鼠出生时看似正常，但由于缺乏双糖链蛋白聚糖，表现出以生长速率降低和骨量减少为特征的表型。据我们所知，这是第一份关于非胶原蛋白ECM蛋白缺乏导致骨骼表型的报道，该表型以低骨量为特征，且随着年龄增长而愈发明显。这些小鼠可作为研究ECM蛋白在骨质疏松症中作用的动物模型。
