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G-protein stimulatory subunit alpha and Gq/11α G-proteins are both required to maintain quiescent stem-like chondrocytes

Author

Listed:
  • Andrei S. Chagin

    (Karolinska Institutet
    Endocrine Unit, Massachusetts General Hospital and Harvard Medical School)

  • Karuna K. Vuppalapati

    (Karolinska Institutet)

  • Tatsuya Kobayashi

    (Endocrine Unit, Massachusetts General Hospital and Harvard Medical School)

  • Jun Guo

    (Endocrine Unit, Massachusetts General Hospital and Harvard Medical School)

  • Takao Hirai

    (Endocrine Unit, Massachusetts General Hospital and Harvard Medical School)

  • Min Chen

    (Metabolic Disease Branch, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health)

  • Stefan Offermanns

    (Max-Planck-Institute for Heart and Lung Research)

  • Lee S. Weinstein

    (Metabolic Disease Branch, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health)

  • Henry M. Kronenberg

    (Endocrine Unit, Massachusetts General Hospital and Harvard Medical School)

Abstract

Round chondrocytes in the resting zone of the growth plate provide precursors for columnar chondrocytes and have stem-like properties. Here we demonstrate that these stem-like chondrocytes undergo apoptosis in the absence of the receptor (PPR) for parathyroid hormone-related protein. We examine the possible roles of heterotrimeric G-proteins activated by the PPR. Inactivation of the G-protein stimulatory α-subunit (Gsα) leads to accelerated differentiation of columnar chondrocytes, as seen in the PPR knockout, but a remnant of growth cartilage remains, in contrast to disappearance of the growth cartilage in the PPR knockout. Stem-like chondrocytes lose their quiescence and proliferate upon Gsα ablation. Inactivation of Gsα in mice with a mutant PPR that cannot activate G proteins, Gq and G11, leads to a PPR knockout-like phenotype. Thus, Gsα is the major mediator of the anti-differentiation action of the PPR, while activation of both Gsα and Gq/11α is required for quiescence of stem-like chondrocytes.

Suggested Citation

  • Andrei S. Chagin & Karuna K. Vuppalapati & Tatsuya Kobayashi & Jun Guo & Takao Hirai & Min Chen & Stefan Offermanns & Lee S. Weinstein & Henry M. Kronenberg, 2014. "G-protein stimulatory subunit alpha and Gq/11α G-proteins are both required to maintain quiescent stem-like chondrocytes," Nature Communications, Nature, vol. 5(1), pages 1-14, May.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms4673
    DOI: 10.1038/ncomms4673
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