Journal article
ADAM17 Controls Endochondral Ossification by Regulating Terminal Differentiation of Chondrocytes
Molecular and cellular biology, Vol.33(16), pp.3077-3090
08/15/2013
DOI: 10.1128/MCB.00291-13
PMCID: PMC3753912
PMID: 23732913
Abstract
ABSTRACT Endochondral ossification is a highly regulated process that relies on properly orchestrated cell-cell interactions in the developing growth plate. This study is focused on understanding the role of a crucial regulator of cell-cell interactions, the membrane-anchored metalloproteinase ADAM17, in endochondral ossification. ADAM17 releases growth factors, cytokines, and other membrane proteins from cells and is essential for epidermal growth factor receptor (EGFR) signaling and for processing tumor necrosis factor alpha. Here, we report that mice lacking ADAM17 in chondrocytes ( A17ΔCh ) have a significantly expanded zone of hypertrophic chondrocytes in the growth plate and retarded growth of long bones. This abnormality is caused by an accumulation of the most terminally differentiated type of chondrocytes that produces a calcified matrix. Inactivation of ADAM17 in osteoclasts or endothelial cells does not affect the zone of hypertrophic chondrocytes, suggesting that the main role of ADAM17 in the growth plate is in chondrocytes. This notion is further supported by in vitro experiments showing enhanced hypertrophic differentiation of primary chondrocytes lacking Adam17 . The enlarged zone of hypertrophic chondrocytes in A17ΔCh mice resembles that described in mice with mutant EGFR signaling or lack of its ligand transforming growth factor α (TGFα), suggesting that ADAM17 regulates terminal differentiation of chondrocytes during endochondral ossification by activating the TGFα/EGFR signaling axis.
Details
- Title: Subtitle
- ADAM17 Controls Endochondral Ossification by Regulating Terminal Differentiation of Chondrocytes
- Creators
- Katherine C Hall - Arthritis and Tissue Degeneration Program, The Hospital for Special Surgery, New York, New York, USA, Department of Cell and Developmental Biology, Weill Cornell Medical College, New York, New York, USADaniel Hill - Arthritis and Tissue Degeneration Program, The Hospital for Special Surgery, New York, New York, USAMiguel Otero - Tissue Engineering Repair and Regeneration Program, The Hospital for Special Surgery, New York, New York, USADarren A Plumb - Tissue Engineering Repair and Regeneration Program, The Hospital for Special Surgery, New York, New York, USADara Froemel - Arthritis and Tissue Degeneration Program, The Hospital for Special Surgery, New York, New York, USACecilia L Dragomir - Tissue Engineering Repair and Regeneration Program, The Hospital for Special Surgery, New York, New York, USAThorsten Maretzky - Arthritis and Tissue Degeneration Program, The Hospital for Special Surgery, New York, New York, USAAdele Boskey - Musculoskeletal Integrity Program, The Hospital for Special Surgery, New York, New York, USA, Departments of Medicine and of Physiology, Biophysics and Systems Biology Program, Weill Cornell Medical College, New York, New York, USAHoward C Crawford - Department of Cancer Biology, Mayo Clinic Cancer Center, Jacksonville, Florida, USALicia Selleri - Department of Cell and Developmental Biology, Weill Cornell Medical College, New York, New York, USAMary B Goldring - Department of Cell and Developmental Biology, Weill Cornell Medical College, New York, New York, USA, Tissue Engineering Repair and Regeneration Program, The Hospital for Special Surgery, New York, New York, USA, Departments of Medicine and of Physiology, Biophysics and Systems Biology Program, Weill Cornell Medical College, New York, New York, USACarl P Blobel - Arthritis and Tissue Degeneration Program, The Hospital for Special Surgery, New York, New York, USA, Department of Cell and Developmental Biology, Weill Cornell Medical College, New York, New York, USA, Departments of Medicine and of Physiology, Biophysics and Systems Biology Program, Weill Cornell Medical College, New York, New York, USA
- Resource Type
- Journal article
- Publication Details
- Molecular and cellular biology, Vol.33(16), pp.3077-3090
- DOI
- 10.1128/MCB.00291-13
- PMID
- 23732913
- PMCID
- PMC3753912
- NLM abbreviation
- Mol Cell Biol
- ISSN
- 0270-7306
- eISSN
- 1098-5549
- Language
- English
- Date published
- 08/15/2013
- Academic Unit
- Internal Medicine
- Record Identifier
- 9984094536302771
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