title: MiR-630 Inhibits Endothelial-Mesenchymal Transition by Targeting Slug in Traumatic Heterotopic Ossification.
abstract: Heterotopic ossification (HO) is the abnormal formation of mature bone in extraskeletal soft tissues that occurs as a result of inflammation caused by traumatic injury or associated with genetic mutation. Despite extensive research to identify the source of osteogenic progenitors, the cellular origins of HO are controversial and the underlying mechanisms, which are important for the early detection of HO, remain unclear. Here, we used in vitro and in vivo models of BMP4 and TGF-β2-induced HO to identify the cellular origin and the mechanisms mediating the formation of ectopic bone in traumatic HO. Our results suggest an endothelial origin of ectopic bone in early phase of traumatic HO and indicate that the inhibition of endothelial-mesenchymal transition by miR-630 targeting Slug plays a role in the formation of ectopic bone in HO. A matched case-control study showed that miR-630 is specifically downregulated during the early stages of HO and can be used to distinguish HO from other processes leading to bone formation. Our findings suggest a potential mechanism of post-traumatic ectopic bone formation and identify miR-630 as a potential early indicator of HO.
authors.affiliation: Department of Orthopaedics, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai, 200233, China.
authors.forename: Yangbai
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Orthopaedics, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai, 200233, China.
authors.forename: Jiangyu
authors.initials: J
authors.lastname: Cai
authors.affiliation: Department of Orthopaedics, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai, 200233, China.
authors.forename: Shiyang
authors.initials: S
authors.lastname: Yu
authors.affiliation: Department of Orthopaedics, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai, 200233, China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Chen
authors.affiliation: Department of Orthopaedics, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai, 200233, China.
authors.forename: Fengfeng
authors.initials: F
authors.lastname: Li
authors.affiliation: Department of Orthopaedics, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai, 200233, China.
authors.forename: Cunyi
authors.initials: C
authors.lastname: Fan
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D016022:Case-Control Studies; D002648:Child; D004727:Endothelium / Q000502:physiology*; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D008648:Mesoderm / Q000502:physiology*; D008807:Mice, Inbred BALB C; D035683:MicroRNAs / Q000378:metabolism*; D008875:Middle Aged; D009999:Ossification, Heterotopic; D000071250:Snail Family Transcription Factors / Q000378:metabolism*; D014947:Wounds and Injuries / Q000150:complications*; D055815:Young Adult
chemical_list: C548399:MIRN630 microRNA, human; D035683:MicroRNAs; C000604407:SNAI1 protein, human; D000071250:Snail Family Transcription Factors