Multipotent progenitors resident in the skeletal muscle interstitium exhibit robust BMP-dependent osteogenic activity and mediate heterotopic ossification.
Multipotent progenitors resident in the skeletal muscle interstitium exhibit robust BMP-dependent osteogenic activity and mediate heterotopic ossification.
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DOI：
10.1002/jbmr.1562
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发表时间：
2012-05
期刊：
影响因子：
--
通讯作者：
Goldhamer DJ
中科院分区：
文献类型：
--
作者：
Wosczyna MN;Biswas AA;Cogswell CA;Goldhamer DJ
异位骨化是一种使人衰弱的疾病，可由创伤性损伤、手术或遗传疾病引起。我们通过肌内移植的异位骨化的谱系追踪和生物测定研究了小鼠异位骨骼发生的细胞起源。我们鉴定、表征和纯化了一个组织驻留的干/祖细胞群体，该群体表现出强大的成骨潜力，并代表了异位骨化的主要来源细胞。这些祖细胞存在于骨骼肌和其他组织的骨组织中，并且与内皮不同，内皮对BMP 2刺激不表现出成骨活性。肌内移植与培养中的克隆分析一起显示，这些祖细胞是多能的，表现出BMP依赖性的成骨分化和自发成脂分化的能力。鉴定负责异位骨化的起源细胞为治疗、减轻或预防这种致残性疾病提供了潜在的治疗靶点。
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 identify, characterize and purify 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 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.
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