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Effects of Ca2+ sensing receptor activation in the growth plate

Shufang Wu1, Teresa Palese, Om Prakash Mishra

  • 1Section of Endocrinology and Diabetes, Drexel University College of Medicine, St. Christopher's Hospital for Children, Philadelphia, Pennsylvania 19134, USA.

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
|November 5, 2003
PubMed

Insights

The Ca2+-sensing receptor (CaR) activates growth plate chondrogenesis, accelerating longitudinal bone growth. This study demonstrates CaR agonist use promotes skeletal development by enhancing chondrocyte differentiation and proliferation.

Area of Science:

  • Endocrinology
  • Developmental Biology
  • Skeletal Biology

Background:

  • The Ca2+-sensing receptor (CaR), a G protein-coupled receptor, is present in mammalian growth plates.
  • CaR knockout mice show growth retardation, but confounding factors like hyperparathyroidism complicate interpretation.
  • The precise role of CaR in growth plate chondrogenesis and longitudinal bone growth remains unclear.

Purpose of the Study:

  • To investigate the role of CaR in regulating growth plate chondrogenesis and longitudinal bone growth.
  • To determine if CaR activation influences chondrocyte differentiation and proliferation in the growth plate.

Main Methods:

  • Organ culture of fetal rat metatarsal bones (dpc 20) in serum-free medium for 7 days.
  • Treatment with NPS-R-568, a CaR agonist, at 10 nM.
  • Assessment of longitudinal growth, growth plate zone heights, collagen X expression (immunohistochemistry), and thymidine incorporation.

Main Results:

  • CaR agonist NPS-R-568 significantly increased cumulative longitudinal growth of metatarsal explants.
  • NPS-R-568 enhanced the height of the hypertrophic zone and collagen X expression, indicating increased chondrocyte differentiation.
  • NPS-R-568 also increased the height of the proliferative zone and thymidine incorporation, suggesting enhanced chondrocyte proliferation.

Conclusions:

  • Activation of the Ca2+-sensing receptor in the growth plate accelerates longitudinal bone growth.
  • CaR signaling promotes skeletal development by stimulating chondrogenesis, including both chondrocyte differentiation and proliferation.

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