State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200031, China.
Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY 10065, USA.
Sci Adv. 2020 Nov 4;6(45). doi: 10.1126/sciadv.aaz1410. Print 2020 Nov.
Bone fracture is repaired predominantly through endochondral ossification. However, the regulation of endochondral ossification by key factors during fracture healing remains largely enigmatic. Here, we identify histone modification enzyme LSD1 as a critical factor regulating endochondral ossification during bone regeneration. Loss of LSD1 in lineage cells severely impaired bone fracture healing. Mechanistically, LSD1 tightly controls retinoic acid signaling through regulation of expression level. The increased retinoic acid signaling in LSD1-deficient mice suppressed SOX9 expression and impeded the cartilaginous callus formation during fracture repair. The discovery that LSD1 can regulate endochondral ossification during fracture healing will benefit the understanding of bone regeneration and have implications for regenerative medicine.
骨骨折主要通过软骨内骨化修复。然而，在骨折愈合过程中，关键因子对软骨内骨化的调控在很大程度上仍是个谜。在这里，我们发现组蛋白修饰酶 LSD1 是调节骨再生过程中软骨内骨化的关键因素。谱系细胞中 LSD1 的缺失严重损害了骨骨折愈合。在机制上，LSD1 通过调节表达水平来紧密控制维甲酸信号。在 LSD1 缺陷小鼠中，增加的维甲酸信号抑制了 SOX9 的表达，并阻碍了骨折修复过程中的软骨痂形成。发现 LSD1 可以调节骨折愈合过程中的软骨内骨化，将有助于理解骨再生，并对再生医学具有重要意义。
