Department of Developmental Biology, Faculty of Biology and Centre for Medical Biotechnology, University Duisburg-Essen, Essen, Germany.
Matrix Biol. 2014 Feb;34:55-63. doi: 10.1016/j.matbio.2013.11.003. Epub 2013 Dec 24.
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都是通过软骨内骨化形成的。这一过程始于间充质细胞的凝聚和分化为软骨细胞。这些软骨细胞经历了几个分化步骤，从增殖到肥大软骨细胞，随后被骨取代。软骨细胞的增殖和分化受到信号分子的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 HS 在调节骨形成中的作用的最新认识。在人类中，HS 合成酶 Ext1 和 Ext2 的突变会导致多发性软骨瘤综合征，这是一种骨骼疾病，其特征是身材矮小和良性软骨帽肿瘤的形成。我们回顾了目前对疾病起源的认识，并讨论了其可能的分子基础。此外，我们总结了 HS 作为发育中骨骼信号转导和信号强度调节剂的作用的现有认识。
