title: Yap1 Regulates Multiple Steps of Chondrocyte Differentiation during Skeletal Development and Bone Repair.
abstract: Hippo signaling controls organ size and tissue regeneration in many organs, but its roles in chondrocyte differentiation and bone repair remain elusive. Here, we demonstrate that Yap1, an effector of Hippo pathway inhibits skeletal development, postnatal growth, and bone repair. We show that Yap1 regulates chondrocyte differentiation at multiple steps in which it promotes early chondrocyte proliferation but inhibits subsequent chondrocyte maturation both in vitro and in vivo. Mechanistically, we find that Yap1 requires Teads binding for direct regulation of Sox6 expression to promote chondrocyte proliferation. In contrast, Yap1 inhibits chondrocyte maturation by suppression of Col10a1 expression through interaction with Runx2. In addition, Yap1 also governs the initiation of fracture repair by inhibition of cartilaginous callus tissue formation. Taken together, our work provides insights into the mechanism by which Yap1 regulates endochondral ossification, which may help the development of therapeutic treatment for bone regeneration.
authors.affiliation: Stem Cell and Regeneration Thematic Research Program, School of Biomedical Sciences, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, China.
authors.forename: Yujie
authors.initials: Y
authors.lastname: Deng
authors.affiliation: Life Sciences Institute and Innovation Center for Cell Signaling Network, Zhejiang University, Hangzhou 310058, China.
authors.forename: Ailing
authors.initials: A
authors.lastname: Wu
authors.affiliation: Transgenic Core, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, China.
authors.forename: Pikshan
authors.initials: P
authors.lastname: Li
authors.affiliation: Stem Cells and Regeneration Medicine Laboratory, Department of Orthopaedics & Traumatology, Li Ka Shing Institute of Health Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Li
authors.affiliation: Musculoskeletal Research Laboratory, Department of Orthopaedics & Traumatology, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Qin
authors.affiliation: Life Sciences Institute and Innovation Center for Cell Signaling Network, Zhejiang University, Hangzhou 310058, China.
authors.forename: Hai
authors.initials: H
authors.lastname: Song
authors.affiliation: Ministry of Education Key Laboratories for Regenerative Medicine, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, China; Stem Cell and Regeneration Thematic Research Program, School of Biomedical Sciences, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, China; School of Biomedical Sciences Core Laboratory, Shenzhen Research Institute, The Chinese University of Hong Kong, Shenzhen 518057, China. Electronic address: kmak@cuhk.edu.hk.
authors.forename: Kinglun Kingston
authors.initials: KK
authors.lastname: Mak
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000502:physiology*; D000818:Animals; D018797:Cell Cycle Proteins; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D019902:Chondrocytes / Q000502:physiology*; D005260:Female; D005269:Femur / Q000254:growth & development / Q000503:physiopathology; D017102:Fracture Healing; D005786:Gene Expression Regulation; D008822:Mice, Transgenic; D010012:Osteogenesis; D010750:Phosphoproteins / Q000502:physiology*; D011485:Protein Binding; D055755:SOXD Transcription Factors / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D000091102:YAP-Signaling Proteins
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins; D010750:Phosphoproteins; D055755:SOXD Transcription Factors; C095939:Sox6 protein, mouse; D000091102:YAP-Signaling Proteins; C486223:Yap1 protein, mouse