骨发育,增长,修复是复杂的过程,涉及各种细胞类型和相互作用,骨骼干细胞和祖细胞发挥着核心作用。最近的研究为介导膜内和软骨内骨发育的骨骼前体群体带来了新的见解。在以后的生活中,许多决定发育的细胞和分子机制在骨折后被重新激活,与强大的创伤诱导的信号线索触发各种出生后骨骼干/祖细胞(SSPC)居住在骨缺损附近。有趣的是,在这种伤害的背景下,目前的证据表明,SSPC和分化的骨骼细胞的命运可以相当灵活和动态,并且可以激活多种细胞来源以作为产生软骨细胞和/或成骨细胞的功能祖细胞。体内谱系追踪的联合实施,基于细胞表面标记的选择,单细胞分子分析,高分辨率原位成像极大地改善了我们对发育和修复性茎/祖细胞亚群的多样性和作用的认识,同时也揭示了它们动态的复杂性,层次结构,和关系。尽管目前还不完全了解,支持谱系灵活性和成骨细胞来源之间可能的可塑性的发现挑战了单一原始的经典教条,自我更新,多能干细胞驱动骨组织形成和再生从一个分层和严格单向分化树的顶点。我们在这里回顾该领域的状况和起源的最新发现,身份,骨骼祖细胞在骨骼发育和生长过程中的命运,讨论成人SSPC人群对骨折修复的贡献,并反思骨骼前体和分化细胞谱系之间的动力学和关系。进一步的研究旨在揭示SSPC的异质性和能力,以及决定其命运和运作的监管线索,将为临床转化为受损的骨折愈合和骨再生医学提供重要的新选择。
骨骼祖细胞对骨骼发育和生长至关重要,因为它们提供细胞构建块(软骨细胞和成骨细胞),形成骨骼组成的软骨和骨组织。在成人生活中,骨折的发生重新激活了类似的组织形成机制,从创伤开始,引发位于骨缺损附近的各种出生后骨骼干/祖细胞(SSPC)分裂和迁移。这些细胞随后通过分化成成熟的软骨细胞和/或成骨细胞而产生功能性骨折修复细胞。近年来,各种先进的研究方法和新技术的结合使用极大地改善了我们对起源的认识,身份,命运,以及发育和修复性骨骼干细胞和祖细胞亚群的作用。同时,这项研究还揭示了它们动力学的相当复杂,多样性,层次结构,和关系,目前还没有完全理解。在这次审查中,我们讨论了该领域的状况以及骨骼干细胞和祖细胞介导骨骼发育的身份和作用的最新发现,增长,和修复。对这些细胞群的进一步研究,包括确定它们的确切性质,命运,和功能,以及如何收获和调节它们,对于开发治疗不愈合骨折的新疗法至关重要。
Bone development, growth, and repair are complex processes involving various cell types and interactions, with central roles played by skeletal stem and progenitor cells. Recent research brought new insights into the skeletal precursor populations that mediate intramembranous and endochondral bone development. Later in life, many of the cellular and molecular mechanisms determining development are reactivated upon fracture, with powerful trauma-induced signaling cues triggering a variety of postnatal skeletal stem/progenitor cells (SSPCs) residing near the bone defect. Interestingly, in this injury context, the current evidence suggests that the fates of both SSPCs and differentiated skeletal cells can be considerably flexible and dynamic, and that multiple cell sources can be activated to operate as functional progenitors generating chondrocytes and/or osteoblasts. The combined implementation of in vivo lineage tracing, cell surface marker-based cell selection, single-cell molecular analyses, and high-resolution in situ imaging has strongly improved our insights into the diversity and roles of developmental and reparative stem/progenitor subsets, while also unveiling the complexity of their dynamics, hierarchies, and relationships. Albeit incompletely understood at present, findings supporting lineage flexibility and possibly plasticity among sources of osteogenic cells challenge the classical dogma of a single primitive, self-renewing, multipotent stem cell driving bone tissue formation and regeneration from the apex of a hierarchical and strictly unidirectional differentiation tree. We here review the state of the field and the newest discoveries in the origin, identity, and fates of skeletal progenitor cells during bone development and growth, discuss the contributions of adult SSPC populations to fracture repair, and reflect on the dynamism and relationships among skeletal precursors and differentiated cell lineages. Further research directed at unraveling the heterogeneity and capacities of SSPCs, as well as the regulatory cues determining their fate and functioning, will offer vital new options for clinical translation toward compromised fracture healing and bone regenerative medicine.
Skeletal progenitor cells are crucial for bone development and growth, as they provide the cellular building blocks (chondrocytes and osteoblasts) that form the cartilage and bone tissues that the skeleton is composed of. In adult life, the occurrence of a bone fracture reactivates similar tissue-forming mechanisms, starting with the trauma triggering various postnatal skeletal stem/progenitor cells (SSPCs) residing near the bone defect to divide and migrate. These cells subsequently generate functional fracture-repairing cells by differentiating into mature chondrocytes and/or osteoblasts. In recent years, the combined use of various advanced research approaches and new techniques has strongly improved our insights into the origin, identity, fates, and roles of developmental and reparative skeletal stem cells and progenitor subsets. Concomitantly, this research also unveiled considerable complexity in their dynamics, diversity, hierarchies, and relationships, which is incompletely understood at present. In this review, we discuss the state of the field and the newest discoveries in the identity and roles of skeletal stem and progenitor cells mediating bone development, growth, and repair. Further research on these cell populations, including determining their exact nature, fate, and functioning, and how they can be harvested and regulated, is critical to develop new treatments for non-healing fractures.