1. Academic Validation
  2. Histone demethylase LSD1 is critical for endochondral ossification during bone fracture healing

Histone demethylase LSD1 is critical for endochondral ossification during bone fracture healing

  • Sci Adv. 2020 Nov 4;6(45):eaaz1410. doi: 10.1126/sciadv.aaz1410.
Jun Sun 1 2 Heng Feng 1 Wenhui Xing 1 Yujiao Han 1 Jinlong Suo 1 Alisha R Yallowitz 2 Niandong Qian 3 Yujiang Shi 4 Matthew B Greenblatt 2 Weiguo Zou 5
Affiliations

Affiliations

  • 1 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.
  • 2 Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY 10065, USA.
  • 3 Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases with Integrated Chinese-Western Medicine, Shanghai Institute of Traumatology and Orthopedics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin 2nd Road, Shanghai 200025, China.
  • 4 Newborn Medicine Division, Boston Children's Hospital and Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
  • 5 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. [email protected].
Abstract

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 Prx1 lineage cells severely impaired bone fracture healing. Mechanistically, LSD1 tightly controls retinoic acid signaling through regulation of Aldh1a2 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.

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