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SOXC Genes and the Control of Skeletogenesis

  • Skeletal Development (E Schipani and E Zelzer, Section Editors)
  • Published:
Current Osteoporosis Reports Aims and scope Submit manuscript

Abstract

The SOXC group of transcription factors, composed of SOX4, SOX11, and SOX12, has evolved to fulfill key functions in cell fate determination. Expressed in many types of progenitor/stem cells, including skeletal progenitors, SOXC proteins potentiate pathways critical for cell survival and differentiation. As skeletogenesis unfolds, SOXC proteins ensure cartilage primordia delineation by amplifying canonical WNT signaling and antagonizing the chondrogenic action of SOX9 in perichondrium and presumptive articular joint cells. They then ensure skeletal elongation by inducing growth plate formation via enabling non-canonical WNT signaling. Human studies have associated SOX4 with bone mineral density and fracture risk in osteoporotic patients, and SOX11 with Coffin-Siris, a syndrome that includes skeletal dysmorphism. Meanwhile, in vitro and mouse studies have suggested important cell-autonomous roles for SOXC proteins in osteoblastogenesis. We here review current knowledge and gaps in understanding of SOXC protein functions, with an emphasis on the skeleton and possible links to osteoporosis.

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Acknowledgments

Work in the Lefebvre lab was supported by the NIH grants AR54513, AR46249, and AR60016 (to VL) and an Arthritis National Research Foundation grant (to PB).

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  1. Department of Cellular & Molecular Medicine, Orthopaedic and Rheumatologic Research Center, Cleveland Clinic Lerner Research Institute, 9500 Euclid Avenue, Cleveland, OH, 44195, USA

    Véronique Lefebvre & Pallavi Bhattaram

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  1. Véronique Lefebvre
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Correspondence to Véronique Lefebvre.

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V. Lefebvre and P. Bhattaram both declare that they have no conflicts of interest.

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All animal studies carried by the authors were performed as approved by the Cleveland Clinic Institutional Animal Care and Use Committee. No studies were conducted by the authors using human subjects or materials.

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This article is part of the Topical Collection on Skeletal Development

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Lefebvre, V., Bhattaram, P. SOXC Genes and the Control of Skeletogenesis. Curr Osteoporos Rep 14, 32–38 (2016). https://doi.org/10.1007/s11914-016-0296-1

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