Department of Molecular and Cell Biology, Center for Regenerative Biology, University of Connecticut Stem Cell Institute, University of Connecticut, Storrs, CT, USA.
J Bone Miner Res. 2012 May;27(5):1004-17. doi: 10.1002/jbmr.1562.
Heterotopic ossification is a debilitating condition that can result from traumatic injury, surgery, or genetic disease. We investigated the cellular origins of heterotopic skeletogenesis in the mouse using lineage tracing and bioassays of heterotopic ossification based on intramuscular transplantation. We identified, characterized, and purified a tissue-resident stem/progenitor cell population that exhibits robust osteogenic potential and represents a major cell-of-origin for heterotopic ossification. These progenitors reside in the interstitium of skeletal muscle and other tissues, and are distinct from the endothelium, which does not exhibit osteogenic activity in response to bone morphogenetic protein 2 (BMP2) stimulation. Intramuscular transplantation, together with clonal analysis in culture, revealed that these progenitors are multipotent, exhibiting the capacity for both BMP-dependent skeletogenic differentiation and spontaneous adipogenic differentiation. Identifying the cells-of-origin responsible for heterotopic ossification provides a potential therapeutic target to treat, mitigate, or prevent this disabling condition.
异位骨化是一种使人衰弱的病症，可能由创伤、手术或遗传疾病引起。我们使用谱系追踪和基于肌肉内移植的异位骨化的生物测定研究了小鼠异位骨骼生成的细胞起源。我们鉴定、表征和纯化了一个组织驻留的干细胞/祖细胞群，该细胞群具有强大的成骨潜能，是异位骨化的主要细胞起源。这些祖细胞存在于骨骼肌和其他组织的间质中，与内皮细胞不同，内皮细胞在骨形态发生蛋白 2 (BMP2)刺激下没有成骨活性。肌肉内移植和培养中的克隆分析表明，这些祖细胞是多能的，表现出 BMP 依赖性成骨分化和自发脂肪生成分化的能力。鉴定出导致异位骨化的细胞起源为治疗、减轻或预防这种致残疾病提供了一个潜在的治疗靶点。
