Parathyroid hormone-related peptide regulation of chick tibial growth plate chondrocyte maturation requires protein kinase A

Michael J. Zuscik, Regis J. O'Keefe, Thomas E. Gunter, J. Edward Puzas, Edward M. Schwarz, Randy N. Rosier

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

Regulation of phenotype in chick tibial growth plate chondrocytes (GPCs) by parathyroid hormone-related peptide (PTHrP) is facilitated via signaling through three pathways: protein kinase A (PKA), protein kinase C (PKC) and inositol-1,4,5-trisphosphate-induced Ca2+ transients. To establish the underlying signaling specificity for PTHrP-regulation of chondrocyte maturation, we examined the separate involvement of each of these three pathways in the PTHrP regulation of key hallmarks of GPC phenotype: stimulation of proliferation and proteoglycan synthesis and reduction of alkaline phosphatase activity and type X collagen expression. Mimicking the PTHrP stimulation either of PKC with 1-oleoyl 2-acetyl glycerol or of a Ca2+ pulse with 65 mM KCl did not lead to PTHrP-like effects on any of the four markers examined. Also, inhibition of PKC with myr-ψPKC or blockade of Ca2+ signals with an intracellular chelator did not inhibit PTHrP action. However, PKA activation with dibutyryl cAMP mimicked PTHrP and blockade of PTHrP stimulation of PKA with H-89 inhibited the regulatory action of the factor. These data demonstrate that although activation of PKC or Ca2+ signals is not required, the cylic AMP-dependent A kinase is required for PTHrP to regulate key hallmarks of GPC phenotype.

Original languageEnglish
Pages (from-to)1079-1090
Number of pages12
JournalJournal of Orthopaedic Research
Volume20
Issue number5
DOIs
StatePublished - Jan 1 2002
Externally publishedYes

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