Mouse Digit Tip Regeneration Is Mechanical Load Dependent.

Mouse Digit Tip Regeneration Is Mechanical Load Dependent.
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DOI:
10.1002/jbmr.4470
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发表时间:
2022-03
期刊:
Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research
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其他
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小鼠趾尖的截肢导致芽细胞介导的再生。在该模型中,新骨重新生长以延长截肢的残端骨,导致末端指骨元件沿着与相关的非骨骼组织的功能性替换。众所周知,骨修复的生理学实例,如牵张成骨和骨折修复,需要机械载荷。然而,在哺乳动物趾尖再生过程中机械负荷的作用是未知的。在这项研究中,我们证明,减少机械负荷抑制芽基形成衰减骨吸收和伤口愈合,导致在手指再生的完全抑制。当机械负荷恢复时,机械卸载对伤口愈合和再生的影响是完全可逆的。芽基形成后的机械卸载导致从头骨形成的速率降低,表明骨再生反应的机械负荷依赖性。此外,使用氰基丙烯酸酯组织粘合剂Dermabond增强机械卸载手指的伤口愈合反应,可改善伤口闭合并部分挽救指尖再生。两者合计,这些结果表明,哺乳动物趾尖再生是机械负荷依赖性的。鉴于人类指尖再生与小鼠指尖有许多共同的特征,这些结果将机械负荷确定为人类从头骨再生的先前未被认识到的要求。
Amputation of the mouse digit tip results in blastema-mediated regeneration. In this model, new bone regenerates de novo to lengthen the amputated stump bone, resulting in a functional replacement of the terminal phalangeal element along with associated non-skeletal tissues. Physiological examples of bone repair, such as distraction osteogenesis and fracture repair, are well known to require mechanical loading. However, the role of mechanical loading during mammalian digit tip regeneration is unknown. In this study, we demonstrate that reducing mechanical loading inhibits blastema formation by attenuating bone resorption and wound closure, resulting in the complete inhibition of digit regeneration. Mechanical unloading effects on wound healing and regeneration are completely reversible when mechanical loading is restored. Mechanical unloading after blastema formation results in a reduced rate of de novo bone formation, demonstrating mechanical load dependence of the bone regenerative response. Moreover, enhancing the wound-healing response of mechanically unloaded digits with the cyanoacrylate tissue adhesive Dermabond improves wound closure and partially rescues digit tip regeneration. Taken together, these results demonstrate that mammalian digit tip regeneration is mechanical load-dependent. Given that human fingertip regeneration shares many characteristics with the mouse digit tip, these results identify mechanical load as a previously unappreciated requirement for de novo bone regeneration in humans.
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