BMP-9-Induced Muscle Heterotopic Ossification Requires Changes to the Skeletal Muscle Microenvironment
BMP-9-Induced Muscle Heterotopic Ossification Requires Changes to the Skeletal Muscle Microenvironment
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DOI：
10.1002/jbmr.311
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发表时间：
2011-06-01
影响因子：
6.2
通讯作者：
Grenier, Guillaume
中科院分区：
文献类型：
--
作者：
Leblanc, Elisabeth;Trensz, Frederic;Grenier, Guillaume
异位骨化（HO）是指软组织内骨的形成。症状包括关节僵硬、肿胀和疼痛。除了遗传形式，常见的创伤形式通常发生在受损肌肉的损伤部位，并且通常与脑损伤有关。我们研究了骨形态发生蛋白9（BMP-9），它具有很强的骨诱导能力，其参与肌肉HO的生理病理学。我们发现BMP-9通过增加碱性磷酸酶活性和骨特异性标志物表达对小鼠肌肉驻留基质细胞具有骨诱导作用。有趣的是，BMP-9仅在受损肌肉中诱导HO，而BMP-2在骨骼肌中促进HO，而不管其状态如何。添加可溶形式的ALK 1蛋白（BMP-9受体）可显著抑制细胞中BMP-9和受损肌肉中HO的骨诱导潜力。因此，BMP-9应该被认为是参与HO病理生理学的候选者，其活性取决于骨骼肌微环境。(C)2011年美国骨与矿物质研究学会。
Heterotopic ossification (HO) is defined as the formation of bone inside soft tissue. Symptoms include joint stiffness, swelling, and pain. Apart from the inherited form, the common traumatic form generally occurs at sites of injury in damaged muscles and is often associated with brain injury. We investigated bone morphogenetic protein 9 (BMP-9), which possesses a strong osteoinductive capacity, for its involvement in muscle HO physiopathology. We found that BMP-9 had an osteoinductive influence on mouse muscle resident stromal cells by increasing their alkaline phosphatase activity and bone-specific marker expression. Interestingly, BMP-9 induced HO only in damaged muscle, whereas BMP-2 promoted HO in skeletal muscle regardless of its state. The addition of the soluble form of the ALK1 protein (the BMP-9 receptor) significantly inhibited the osteoinductive potential of BMP-9 in cells and HO in damaged muscles. BMP-9 thus should be considered a candidate for involvement in HO physiopathology, with its activity depending on the skeletal muscle microenvironment. (C) 2011 American Society for Bone and Mineral Research.