CXCL12/CXCR4 signaling and other recruitment and homing pathways in fracture repair.
CXCL12/CXCR4 signaling and other recruitment and homing pathways in fracture repair.
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DOI：
10.1038/bonekey.2013.34
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发表时间：
2013-03-13
期刊：
影响因子：
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通讯作者：
Yellowley, Clare
中科院分区：
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作者：
Yellowley, Clare
细胞募集、迁移和归巢到骨折部位对于炎症过程、新血管形成、软骨形成、骨生成和最终骨重建是必不可少的。间充质干细胞（MSC）需要从局部来源，如骨膜和局部骨髓，也可以从循环和远端骨髓招募。虽然局部募集过程可能涉及基质结合和降解，但全身性募集可能利用外渗，这是白细胞离开脉管系统的过程。CXCL 12（基质细胞衍生因子-1（SDF-1））是趋化因子CXC家族的成员，被认为在骨折部位的细胞迁移中起重要作用。然而，在血肿和愈伤组织中有许多上调的分子不仅对炎性细胞而且对内皮细胞和MSC具有趋化潜力。令人惊讶的是，几乎没有直接的数据支持它们在骨愈合过程中的细胞归巢作用。目前用于骨再生的疗法利用局部或全身干细胞移植。最近，一种新的策略，涉及动员大量的内源性干细胞和祖细胞从骨髓进入循环已被证明对骨愈合有积极的影响。对骨折后细胞募集和归巢的分子机制有更全面的了解，将有助于对骨的这种策略进行微调。
Cell recruitment, migration and homing to the fracture site are essential for the inflammatory process, neovascularization, chondrogenesis, osteogenesis and ultimately bone remodeling. Mesenchymal stem cells (MSCs) are required to navigate from local sources such as the periosteum and local bone marrow, and may also be recruited from the circulation and distant bone marrow. While the local recruitment process may involve matrix binding and degradation, systemic recruitment may utilize extravasation, a process used by leukocytes to exit the vasculature. CXCL12 (stromal cell-derived factor-1 (SDF-1)), a member of the CXC family of chemokines, is thought to have an important role in cell migration at the fracture site. However, there are many molecules upregulated in the hematoma and callus that have chemotactic potential not only for inflammatory cells but also for endothelial cells and MSCs. Surprisingly, there is little direct data to support their role in cell homing during bone healing. Current therapeutics for bone regeneration utilize local or systemic stem cell transplantation. More recently, a novel strategy that involves mobilization of large numbers of endogenous stem and progenitor cells from bone marrow into the circulation has been shown to have positive effects on bone healing. A more complete understanding of the molecular mechanisms underlying cell recruitment and homing subsequent to fracture will facilitate the fine-tuning of such strategies for bone.