SOCS2 is the critical regulator of GH action in murine growth plate chondrogenesis

Chloe Pass, Vicky Elizabeth MacRae, Carmen Huesa, S Faisal Ahmed, Colin Farquharson

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Suppressor of Cytokine Signaling-2 (SOCS2) is a negative regulator of growth hormone (GH) signaling and bone growth via inhibition of the Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway. This has been classically demonstrated by the overgrowth phenotype of SOCS2(-/-) mice, which has normal systemic insulin-like growth factor 1 (IGF-1) levels. The local effects of GH on bone growth are equivocal, and therefore this study aimed to understand better the SOCS2 signaling mechanisms mediating the local actions of GH on epiphyseal chondrocytes and bone growth. SOCS2, in contrast to SOCS1 and SOCS3 expression, was increased in cultured chondrocytes after GH challenge. Gain- and loss-of-function studies indicated that GH-stimulated chondrocyte STATs-1, -3, and -5 phosphorylation was increased in SOCS2(-/-) chondrocytes but not in cells overexpressing SOCS2. This increased chondrocyte STAT signaling in the absence of SOCS2 is likely to explain the observed GH stimulation of longitudinal growth of cultured SOCS2(-/-) embryonic metatarsals and the proliferation of chondrocytes within. Consistent with this metatarsal data, bone growth rates, growth plate widths, and chondrocyte proliferation were all increased in SOCS2(-/-) 6-week-old mice as was the number of phosphorylated STAT-5-positive hypertrophic chondrocytes. The SOCS2(-/-) mouse represents a valid model for studying the local effects of GH on bone growth.

Original languageEnglish
Pages (from-to)1055-66
Number of pages12
JournalJournal of Bone and Mineral Research
Volume27
Issue number5
DOIs
Publication statusPublished - May 2012
Externally publishedYes

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Keywords

  • Animals
  • Blotting, Western
  • Cell Proliferation
  • Cells, Cultured
  • Chondrocytes
  • Chondrogenesis
  • Gene Expression Regulation, Developmental
  • Genotype
  • Growth Hormone
  • Growth Plate
  • Immunohistochemistry
  • Insulin-Like Growth Factor I
  • Male
  • Metatarsal Bones
  • Mice
  • Mice, Knockout
  • Phosphorylation
  • Polymerase Chain Reaction
  • STAT Transcription Factors
  • Signal Transduction
  • Suppressor of Cytokine Signaling Proteins
  • Journal Article
  • Research Support, Non-U.S. Gov't

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