Jochmann Katja, Bachvarova Velina, Vortkamp Andrea
Department of Developmental Biology, Faculty of Biology and Centre for Medical Biotechnology, University of Duisburg-Essen, Essen, Germany.
Matrix Biol. 2014 Apr;35:239-47. doi: 10.1016/j.matbio.2014.04.001. Epub 2014 Apr 12.
Most elements of the vertebrate skeleton are formed by endochondral ossification. This process is initiated with mesenchymal cells that condense and differentiate into chondrocytes. These undergo several steps of differentiation from proliferating into hypertrophic chondrocytes, which are subsequently replaced by bone. Chondrocyte proliferation and differentiation are tightly controlled by a complex network of signaling molecules. During recent years, it has become increasingly clear that heparan sulfate (HS) carrying proteoglycans play a critical role in controlling the distribution and activity of these secreted factors. In this review we summarize the current understanding of the role of HS in regulating bone formation. In human, mutations in the HS synthetizing enzymes Ext1 and Ext2 induce the Multiple Osteochondroma syndrome, a skeletal disorder characterized by short stature and the formation of benign cartilage-capped tumors. We review the current insight into the origin of the disease and discuss its possible molecular basis. In addition, we summarize the existing insight into the role of HS as a regulator of signal propagation and signaling strength in the developing skeleton.
脊椎动物骨骼的大多数成分是通过软骨内成骨形成的。这个过程始于间充质细胞，它们凝聚并分化为软骨细胞。这些软骨细胞经历从增殖到肥大软骨细胞的几个分化步骤，随后被骨组织取代。软骨细胞的增殖和分化受到信号分子复杂网络的严格控制。近年来，越来越清楚的是，携带蛋白聚糖的硫酸乙酰肝素（HS）在控制这些分泌因子的分布和活性方面起着关键作用。在这篇综述中，我们总结了目前对HS在调节骨形成中作用的理解。在人类中，HS合成酶Ext1和Ext2的突变会诱发多发性骨软骨瘤综合征，这是一种以身材矮小和形成良性软骨帽状肿瘤为特征的骨骼疾病。我们回顾了目前对该疾病起源的认识，并讨论了其可能的分子基础。此外，我们总结了目前对HS作为发育中骨骼信号传播和信号强度调节剂作用的认识。
