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

J Orthop Res. 2002 Sep;20(5):1079-90. doi: 10.1016/S0736-0266(02)00027-X.

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-psiPKC 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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alkaline Phosphatase / metabolism
  • Animals
  • Bucladesine / pharmacology
  • Calcium / metabolism
  • Calcium Signaling
  • Cells, Cultured
  • Chelating Agents / pharmacology
  • Chickens
  • Chondrocytes / drug effects*
  • Chondrocytes / enzymology
  • Collagen Type X / genetics
  • Collagen Type X / metabolism
  • Cyclic AMP-Dependent Protein Kinases / antagonists & inhibitors
  • Cyclic AMP-Dependent Protein Kinases / metabolism*
  • DNA / biosynthesis
  • Egtazic Acid / analogs & derivatives*
  • Egtazic Acid / pharmacology
  • Enzyme Inhibitors / pharmacology
  • Growth Plate / drug effects*
  • Growth Plate / enzymology
  • Growth Plate / growth & development
  • Isoquinolines / pharmacology
  • Parathyroid Hormone-Related Protein
  • Peptide Hormones / pharmacology*
  • Proteoglycans / biosynthesis
  • RNA, Messenger / metabolism
  • Sulfonamides*
  • Tibia / drug effects
  • Tibia / enzymology
  • Tibia / growth & development

Substances

  • Chelating Agents
  • Collagen Type X
  • Enzyme Inhibitors
  • Isoquinolines
  • Parathyroid Hormone-Related Protein
  • Peptide Hormones
  • Proteoglycans
  • RNA, Messenger
  • Sulfonamides
  • 1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester
  • Egtazic Acid
  • Bucladesine
  • DNA
  • Cyclic AMP-Dependent Protein Kinases
  • Alkaline Phosphatase
  • N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide
  • Calcium