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

Andrei S. Chagin, Karuna K. Vuppalapati, Tatsuya Kobayashi, Jun Guo, Takao Hirai, Min Chen, Stefan Offermanns, Lee S. Weinstein and Henry M. Kronenberg ()
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Andrei S. Chagin: Karolinska Institutet
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

Nature Communications, 2014, vol. 5, issue 1, 1-14

Abstract: 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.

Date: 2014
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DOI: 10.1038/ncomms4673

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