Regulation of Indian hedgehog mRNA levels in chondrocytic cells by ERK1/2 and p38 mitogen-activated protein kinases

Journal of Cellular Physiology
Lick Pui LaiJane Mitchell

Abstract

Indian hedgehog (Ihh) is produced by growth plate pre-hypertrophic chondrocytes, and is an important regulator of endochondral ossification. However, little is known about the regulation of Ihh in chondrocytes. We have examined the role of integrins and mitogen-activated protein (MAP) kinases in Ihh mRNA regulation in CFK-2 chondrocytic cells. Cells incubated with the beta1-integrin blocking antibody had decreased Ihh mRNA levels, which was accompanied by decreases of activated extracellular signal-regulated kinases (ERK1/2) and activated p38 MAPK. Ihh mRNA levels were also inhibited by U0126, a specific MEK1/2 inhibitor, or SB203580, a specific p38 MAPK inhibitor. Cells transfected with constitutively active MEK1 or MKK3 had increased Ihh mRNA levels, which were diminished by dominant-negative MEK1, p38alpha or p38beta. Stimulation of the PTH1R with 10(-8) M rPTH (1-34) resulted in dephosphorylation of ERK1/2 that was evident within 15 min and sustained for 1 h, as well as transient dephosphorylation of p38 MAPK that was maximal after 25 min. PTH stimulation decreased Ihh mRNA levels, and this effect was blocked by transfecting the cells with constitutively active MEK1 but not by MKK3. These studies demonstrated that activatio...Continue Reading

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Citations

May 18, 2013·Journal of Molecular Endocrinology·Richard Barbuto, Jane Mitchell
Mar 25, 2015·Connective Tissue Research·Wei XinFrank Zaucke
Jun 18, 2011·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Kristine D EstradaKaren M Lyons
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Feb 12, 2008·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Chanika PhornphutkulPhilip A Gruppuso
Sep 28, 2005·Journal of Cellular Biochemistry·Lick Pui Lai, Jane Mitchell
Aug 10, 2019·Cancers·Priyanka BhatejaBhuvaneswari Ramaswamy
Dec 24, 2010·American Journal of Physiology. Endocrinology and Metabolism·Jane MitchellKim Sugamori

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