PDF(Pubmed)
Abstract：
The expression of Prx1 has been used as a marker to define the skeletal stem cells (SSCs) populations found within the bone marrow and periosteum that contribute to bone regeneration. However, Prx1 expressing SSCs (Prx1-SSCs) are not restricted to the bone compartments, but are also located within the muscle and able to contribute to ectopic bone formation. Little is known however, about the mechanism(s) regulating Prx1-SSCs that reside in muscle and how they participate in bone regeneration. This study compared both the intrinsic and extrinsic factors of the periosteum and muscle derived Prx1-SSCs and analyzed their regulatory mechanisms of activation, proliferation, and skeletal differentiation. There was considerable transcriptomic heterogeneity in the Prx1-SSCs found in muscle or the periosteum however in vitro cells from both tissues showed tri-lineage (adipose, cartilage and bone) differentiation. At homeostasis, periosteal-derived Prx1 cells were proliferative and low levels of BMP2 were able to promote their differentiation, while the muscle-derived Prx1 cells were quiescent and refractory to comparable levels of BMP2 that promoted periosteal cell differentiation. The transplantation of Prx1-SCC from muscle and periosteum into either the same site from which they were isolated, or their reciprocal sites showed that periosteal cell transplanted onto the surface of bone tissues differentiated into bone and cartilage cells but was incapable of similar differentiation when transplanted into muscle. Prx1-SSCs from the muscle showed no ability to differentiate at either site of transplantation. Both fracture and ten times the BMP2 dose was needed to promote muscle-derived cells to rapidly enter the cell cycle as well as undergo skeletal cell differentiation. This study elucidates the diversity of the Prx1-SSC population showing that cells within different tissue sites are intrinsically different. While muscle tissue must have factors that promote Prx1-SSC to remain quiescent, either bone injury or high levels of BMP2 can activate these cells to both proliferate and undergo skeletal cell differentiation. Finally, these studies raise the possibility that muscle SSCs are potential target for skeletal repair and bone diseases.
摘要：
Prx1的表达已被用作标记以定义在骨髓和骨膜中发现的有助于骨再生的骨骼干细胞（SSC）群体。然而,Prx1表达SSC（Prx1-SSC）不限于骨区室，但也位于肌肉内，能够促进异位骨形成。然而，鲜为人知，关于调节肌肉中Prx1-SSC的机制以及它们如何参与骨再生。这项研究比较了骨膜和肌肉来源的Prx1-SSCs的内在和外在因素，并分析了其激活的调节机制。扩散,和骨骼分化。在肌肉或骨膜中发现的Prx1-SSC存在相当大的转录组异质性，但是来自两种组织的体外细胞均显示出三谱系（脂肪，软骨和骨）分化。在稳态下，骨膜来源的Prx1细胞增殖，低水平的BMP2能够促进其分化，而肌肉来源的Prx1细胞是静止的，并且与促进骨膜细胞分化的BMP2水平相当。将Prx1-SCC从肌肉和骨膜移植到分离它们的同一部位，或它们的相对位点表明，移植到骨组织表面的骨膜细胞分化为骨骼和软骨细胞，但移植到肌肉中时无法类似的分化。来自肌肉的Prx1-SSC在任一移植部位均没有分化能力。需要骨折和十倍的BMP2剂量来促进肌肉来源的细胞快速进入细胞周期以及经历骨骼细胞分化。这项研究阐明了Prx1-SSC群体的多样性，表明不同组织部位的细胞本质上是不同的。虽然肌肉组织必须有促进Prx1-SSC保持静止的因素，骨损伤或高水平的BMP2可以激活这些细胞增殖并进行骨骼细胞分化。最后,这些研究提出了肌肉间充质干细胞是骨骼修复和骨骼疾病的潜在靶点的可能性。
