小鼠软骨内成骨过程中背腹轴的早期测定。

IF 5.9 1区 医学 Q1 ENDOCRINOLOGY & METABOLISM
Sixun Wu, Hirotaka Matsumoto, Jumpei Morita, Mina Yamabe, Azumi Noguchi, Shinsuke Ohba, Noriaki Ono, Yuki Matsushita
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引用次数: 0

摘要

软骨内成骨是一个高度协调的过程,涉及不同的祖细胞群在间质凝聚和随后的软骨基质和软骨膜中,所有这些都驱动骨骼的形成。为了解胎儿骨骼发育而进行的细胞类型特异性谱系追踪揭示了早期骨骼细胞的各种命运。然而,胎儿骨骼细胞的潜在连续和精确的细胞动力学,特别是沿背腹轴,仍然不清楚。在这里,我们表明,在早期发育阶段,时空特异性的骨骼祖细胞以一种在初始发育阶段严格确定的方式对背-腹侧轴做出贡献。利用Fgfr3- creer和Dlx5-creER细胞系进行的谱系追踪实验显示,间充质凝聚中的Fgfr3+细胞专门参与软骨细胞肥大和软骨基质内休息区和增殖区的背侧。这些细胞对骨骼发育做出了背侧限制性贡献,包括生长板软骨细胞、小梁和皮质成骨细胞以及骨髓基质细胞。在间充质凝聚阶段,使用Rosa26iDTA(诱导白喉毒素片段A)等位基因对Fgfr3+细胞进行功能性消融,导致长骨发育严重中断,强调其在启动骨骼生长中不可或缺的作用。总的来说,这些发现表明,在骨骼发育过程中,凝结阶段对骨骼祖细胞的形成和背腹模式的形成至关重要。了解这些机制将有助于深入了解骨骼生长障碍和骨再生的治疗策略。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Early determination of the dorsal-ventral axis in endochondral ossification in mice.

Endochondral ossification is a highly coordinated process involving distinct progenitor cell populations within the mesenchymal condensation and subsequent cartilage anlage and perichondrium, all of which drive skeletal formation. Cell type-specific lineage tracing conducted to understand fetal bone development has revealed various fates of early skeletal cells. However, the underlying continuous and precise cellular dynamics of fetal skeletal cells, particularly along the dorsoventral axis, remain unclear. Here, we show that spatiotemporally specific skeletal progenitor cells in the early developmental stage contribute to the dorsal-ventral axis in a manner that is strictly determined during initial developmental stages. Lineage-tracing experiments using Fgfr3-creER and Dlx5-creER lines revealed that Fgfr3+ cells in mesenchymal condensation exclusively contributed to hypertrophic chondrocytes and the dorsal side of the resting and proliferating zones within the cartilage anlage. These cells made dorsal-restricted contributions to skeletal development, including growth plate chondrocytes, trabecular and cortical osteoblasts, and bone marrow stromal cells. Functional ablation of Fgfr3+ cells using the Rosa26iDTA (inducible diphtheria toxin fragment A) allele during the mesenchymal condensation stage caused severe disruption in long bone development, underscoring its indispensable role in initiating skeletal growth. Collectively, these findings suggest that the condensation stage is pivotal for the formation of skeletal progenitors and dorsoventral patterning during bone development. Understanding these mechanisms will provide insight into skeletal growth disorders and therapeutic strategies for bone regeneration.

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来源期刊
Journal of Bone and Mineral Research
Journal of Bone and Mineral Research 医学-内分泌学与代谢
CiteScore
11.30
自引率
6.50%
发文量
257
审稿时长
2 months
期刊介绍: The Journal of Bone and Mineral Research (JBMR) publishes highly impactful original manuscripts, reviews, and special articles on basic, translational and clinical investigations relevant to the musculoskeletal system and mineral metabolism. Specifically, the journal is interested in original research on the biology and physiology of skeletal tissues, interdisciplinary research spanning the musculoskeletal and other systems, including but not limited to immunology, hematology, energy metabolism, cancer biology, and neurology, and systems biology topics using large scale “-omics” approaches. The journal welcomes clinical research on the pathophysiology, treatment and prevention of osteoporosis and fractures, as well as sarcopenia, disorders of bone and mineral metabolism, and rare or genetically determined bone diseases.
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