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          Institute: MPI für Herz- und Lungenforschung (W. G. Kerckhoff Institut)     Collection: Yearbook_2015     Display Documents

ID: 711919.0, MPI für Herz- und Lungenforschung (W. G. Kerckhoff Institut) / Yearbook_2015
G-protein stimulatory subunit alpha and Gq/11alpha G-proteins are both required to maintain quiescent stem-like chondrocytes
Authors:Chagin, A. S.; Vuppalapati, K. K.; Kobayashi, T.; Guo, J.; Hirai, T.; Chen, M.; Offermanns, S.; Weinstein, L. S.; Kronenberg, H. M.
Date of Publication (YYYY-MM-DD):2014
Title of Journal:Nat Commun
Start Page:3673
Audience:Not Specified
Abstract / Description: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 alpha-subunit (G(s)alpha) 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 G(s)alpha ablation. Inactivation of G(s)alpha in mice with a mutant PPR that cannot activate G proteins, Gq and G11, leads to a PPR knockout-like phenotype. Thus, G(s)alpha is the major mediator of the anti-differentiation action of the PPR, while activation of both G(s)alpha and Gq/11alpha is required for quiescence of stem-like chondrocytes.
External Publication Status:published
Document Type:Article
Communicated by:MPI für Herz- und Lungenforschung
Affiliations:MPI für physiologische und klinische Forschung
External Affiliations:Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm 17177, Sweden. Endocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114-2696, USA. Metabolic Disease Branch, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892-1752, USA. Department of Pharmacology, Max-Planck-Institute for Heart and Lung Research, Bad Nauheim 61231, Germany. %^ 1435822116
Identifiers:ISSN:2041-1723 (Electronic) 2041-1723 (Linking) %R 10.1038/ncomms4673
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