title: Hypertrophic chondrocytes can become osteoblasts and osteocytes in endochondral bone formation.
abstract: According to current dogma, chondrocytes and osteoblasts are considered independent lineages derived from a common osteochondroprogenitor. In endochondral bone formation, chondrocytes undergo a series of differentiation steps to form the growth plate, and it generally is accepted that death is the ultimate fate of terminally differentiated hypertrophic chondrocytes (HCs). Osteoblasts, accompanying vascular invasion, lay down endochondral bone to replace cartilage. However, whether an HC can become an osteoblast and contribute to the full osteogenic lineage has been the subject of a century-long debate. Here we use a cell-specific tamoxifen-inducible genetic recombination approach to track the fate of murine HCs and show that they can survive the cartilage-to-bone transition and become osteogenic cells in fetal and postnatal endochondral bones and persist into adulthood. This discovery of a chondrocyte-to-osteoblast lineage continuum revises concepts of the ontogeny of osteoblasts, with implications for the control of bone homeostasis and the interpretation of the underlying pathological bases of bone disorders.
authors.affiliation: Department of Biochemistry, Li Ka Shing (LKS) Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong;Institute of Orthopaedics, Xi-Jing Hospital, Fourth Military Medical University, Xi'an 710032, China; and.
authors.forename: Liu
authors.initials: L
authors.lastname: Yang
authors.affiliation: Department of Biochemistry, Li Ka Shing (LKS) Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong;
authors.forename: Kwok Yeung
authors.initials: KY
authors.lastname: Tsang
authors.affiliation: Department of Biochemistry, Li Ka Shing (LKS) Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong;
authors.forename: Hoi Ching
authors.initials: HC
authors.lastname: Tang
authors.affiliation: Department of Biochemistry, Li Ka Shing (LKS) Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong;Centre for Reproduction, Development and Growth, LKS Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong.
authors.forename: Danny
authors.initials: D
authors.lastname: Chan
authors.affiliation: Department of Biochemistry, Li Ka Shing (LKS) Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong;Centre for Reproduction, Development and Growth, LKS Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong kathycheah@hku.hk.
authors.forename: Kathryn S E
authors.initials: KS
authors.lastname: Cheah
mesh_terms: D000818:Animals; D001846:Bone Development; D002454:Cell Differentiation; D019070:Cell Lineage; D019902:Chondrocytes / Q000166:cytology*; D051379:Mice; D010006:Osteoblasts / Q000166:cytology*; D010011:Osteocytes / Q000166:cytology*
keywords: bone repair; chondrocyte lineage; osteoblast ontogeny
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