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PTH Stimulated Growth and Decreased Col‐X Deposition are Phosphotidylinositol‐3,4,5 Triphosphate Kinase and Mitogen Activating Protein Kinase Dependent in Avian Sterna
Author(s) -
Harrington Erik Kern,
Coon David J.,
Kern Matthew F.,
Svoboda Kathy K.H.
Publication year - 2010
Publication title -
the anatomical record: advances in integrative anatomy and evolutionary biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.678
H-Index - 62
eISSN - 1932-8494
pISSN - 1932-8486
DOI - 10.1002/ar.21072
Subject(s) - protein kinase a , mapk/erk pathway , kinase , chondrocyte , microbiology and biotechnology , protein kinase b , ly294002 , pi3k/akt/mtor pathway , chemistry , parathyroid hormone , biology , medicine , endocrinology , signal transduction , phosphatidylinositol , biochemistry , calcium , in vitro
Abstract Type X collagen (Col‐X) deposition is a marker of terminal differentiation during chondrogenesis, in addition to appositional growth and apoptosis. The parathyroid hormone/parathyroid hormone related peptide (PTH/PTHrP) receptor, or PPR, is a G‐Protein coupled receptor (GPCR), which activates several downstream pathways, moderating chondrocyte differentiation, including suppression of Col‐X deposition. An Avian sterna model was used to analyze the PPR GPCR downstream kinase role in growth rate and extracellular matrix (ECM) including Col‐II, IX, and X. Phosphatidylinositol kinase (PI3K), mitogen activating protein kinase (MAPK) and protein kinase A (PKA) were inhibited with specific established inhibitors LY294002, PD98059, and H89, respectively to test the hypothesis that they could reverse/inhibit the PTH/PTHrP pathway. Excised E14 chick sterna were PTH treated with or without an inhibitor and compared to controls. Sternal length was measured every 24 hr. Cultured sterna were immuno‐stained using specific antibodies for Col‐II, IX, or X and examined via confocal microscopy. Increased growth in PTH‐treated sterna was MAPK, PI3K, and PKA dose dependent, suggesting growth was regulated through multiple pathways. Col‐X deposition was rescued in PTH‐treated sterna in the presence of PI3K or MAPK inhibitors, but not with the PKA inhibitor. All three inhibitors moderately disrupted Col‐II and Col‐IX deposition. These results suggest that PTH can activate multiple pathways during chondrocyte differentiation. Anat Rec, 2010. © 2009 Wiley‐Liss, Inc.