Kubota Satoshi, Takigawa Masaharu
Department of Biochemistry and Molecular Dentistry, Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
Int Rev Cytol. 2007;257:1-41. doi: 10.1016/S0074-7696(07)57001-4.
Our bones mostly develop through a process called endochondral ossification. This process is initiated in the cartilage prototype of each bone and continues through embryonic and postnatal development until the end of skeletal growth. Therefore, the central regulator of endochondral ossification is the director of body construction, which is, in other words, the determinant of skeletal size and shape. We suggest that CCN2/CTGF/Hcs24 (CCN2) is a molecule that conducts all of the procedures of endochondral ossification. CCN2, a member of the CCN family of novel modulator proteins, displays multiple functions by manipulating the local information network, using its conserved modules as an interface with a variety of other biomolecules. Under a precisely designed four-dimensional genetic program, CCN2 is produced from a limited population of chondrocytes and acts on all of the mesenchymal cells inside the bone callus to promote the integrated growth of the bone. Furthermore, the utility of CCN2 as regenerative therapeutics against connective tissue disorders, such as bone and cartilage defects and osteoarthritis, has been suggested. Over the years, the pathological action of CCN2 has been suggested. Nevertheless, it can also be regarded as another aspect of the physiological and regenerative function of CCN2, which is discussed as well.
我们的骨骼主要通过一种称为软骨内成骨的过程发育而成。这个过程在每块骨头的软骨原型中启动,并贯穿胚胎期和出生后的发育阶段,直至骨骼生长结束。因此,软骨内成骨的核心调节因子是身体构建的指挥者,换言之,就是骨骼大小和形状的决定因素。我们认为CCN2/结缔组织生长因子/Hcs24(CCN2)是一种执行软骨内成骨所有过程的分子。CCN2是新型调节蛋白CCN家族的成员之一,它通过利用其保守结构域作为与多种其他生物分子的接口来操纵局部信息网络,从而发挥多种功能。在精确设计的四维遗传程序下,CCN2由有限数量的软骨细胞产生,并作用于骨痂内的所有间充质细胞,以促进骨骼的整体生长。此外,有人提出CCN2可作为针对结缔组织疾病(如骨和软骨缺损以及骨关节炎)的再生疗法。多年来,CCN2的病理作用已被提出。然而,它也可被视为CCN2生理和再生功能的另一个方面,对此也进行了讨论。