PPARgamma2 Expression in Growth Plate Chondrocytes is Regulated by P38 and GSK-3

Overview

Journal J Cell Mol Med

Specialties Cell Biology
Molecular Biology

Date 2010 Apr 24

PMID 20414969

Citations 7

Authors

Lee-Anne Stanton

Jennifer Ruizhe Li

Frank Beier

Affiliations

Soon will be listed here.

Abstract

Although peroxisome proliferator activated receptor (PPAR)gamma remains a critical regulator of preadipocyte differentiation, new roles have been discovered in inflammation, bone morphogenesis, endothelial function, cancer, longevity and atherosclerosis. Despite the demonstration of PPARgamma expression in chondrocytes, its role and the pathways affecting its expression and activity in chondrocytes remain largely unknown. We investigated the effects of PPARgamma activation on chondrocyte differentiation and its participation in chondrocyte lipid metabolism. PPARgamma2 expression is highly regulated during chondrocyte differentiation in vivo and in vitro PPARgamma activation with troglitazone resulted in increased Indian hedgehog expression and reduced collagen X expression, confirming previously described roles in the inhibition of differentiation. However, the major effect of PPARgamma2 in chondrocytes appears to be on lipid metabolism. During differentiation chondrocytes increase expression of the lipid-associated metabolizing protein, Lpl, which is accompanied by increased gene expression of PPARgamma. PPARgamma expression is suppressed by p38 activity, but requires GSK-3 activity. Furthermore, Lpl expression is regulated by p38 and GSK-3 signalling. This is the first study demonstrating a relationship between PPARgamma2 expression and chondrocyte lipid metabolism and its regulation by p38 and GSK-3 signalling.

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References

Lai L, Mitchell J . Indian hedgehog: its roles and regulation in endochondral bone development. J Cell Biochem. 2005; 96(6):1163-73. DOI: 10.1002/jcb.20635. View

Berger J, Akiyama T, Meinke P . PPARs: therapeutic targets for metabolic disease. Trends Pharmacol Sci. 2005; 26(5):244-51. DOI: 10.1016/j.tips.2005.03.003. View

Escher P, Wahli W . Peroxisome proliferator-activated receptors: insight into multiple cellular functions. Mutat Res. 2000; 448(2):121-38. DOI: 10.1016/s0027-5107(99)00231-6. View

Bordji K, Grillasca J, Gouze J, Magdalou J, Schohn H, Keller J . Evidence for the presence of peroxisome proliferator-activated receptor (PPAR) alpha and gamma and retinoid Z receptor in cartilage. PPARgamma activation modulates the effects of interleukin-1beta on rat chondrocytes. J Biol Chem. 2000; 275(16):12243-50. DOI: 10.1074/jbc.275.16.12243. View

Braissant O, Foufelle F, Scotto C, Dauca M, Wahli W . Differential expression of peroxisome proliferator-activated receptors (PPARs): tissue distribution of PPAR-alpha, -beta, and -gamma in the adult rat. Endocrinology. 1996; 137(1):354-66. DOI: 10.1210/endo.137.1.8536636. View

Shao Y, Wang L, Hicks D, Tarr S, Ballock R . Expression and activation of peroxisome proliferator-activated receptors in growth plate chondrocytes. J Orthop Res. 2005; 23(5):1139-45. DOI: 10.1016/j.orthres.2005.02.011. View

Zhang R, Murakami S, Coustry F, Wang Y, de Crombrugghe B . Constitutive activation of MKK6 in chondrocytes of transgenic mice inhibits proliferation and delays endochondral bone formation. Proc Natl Acad Sci U S A. 2006; 103(2):365-70. PMC: 1326166. DOI: 10.1073/pnas.0507979103. View

Greene M, Blumberg B, MCBRIDE O, Yi H, Kronquist K, Kwan K . Isolation of the human peroxisome proliferator activated receptor gamma cDNA: expression in hematopoietic cells and chromosomal mapping. Gene Expr. 1995; 4(4-5):281-99. PMC: 6134382. View

Agoston H, Khan S, James C, Gillespie J, Serra R, Stanton L . C-type natriuretic peptide regulates endochondral bone growth through p38 MAP kinase-dependent and -independent pathways. BMC Dev Biol. 2007; 7:18. PMC: 1847438. DOI: 10.1186/1471-213X-7-18. View

10.

Poleni P, Bianchi A, Etienne S, Koufany M, Sebillaud S, Netter P . Agonists of peroxisome proliferators-activated receptors (PPAR) alpha, beta/delta or gamma reduce transforming growth factor (TGF)-beta-induced proteoglycans' production in chondrocytes. Osteoarthritis Cartilage. 2006; 15(5):493-505. DOI: 10.1016/j.joca.2006.10.009. View

11.

Vidal-Puig A, Considine R, Jimenez-Linan M, Werman A, Pories W, Caro J . Peroxisome proliferator-activated receptor gene expression in human tissues. Effects of obesity, weight loss, and regulation by insulin and glucocorticoids. J Clin Invest. 1997; 99(10):2416-22. PMC: 508081. DOI: 10.1172/JCI119424. View

12.

Dreyer C, Krey G, Keller H, Givel F, Helftenbein G, Wahli W . Control of the peroxisomal beta-oxidation pathway by a novel family of nuclear hormone receptors. Cell. 1992; 68(5):879-87. DOI: 10.1016/0092-8674(92)90031-7. View

13.

Ross S, Hemati N, Longo K, Bennett C, Lucas P, Erickson R . Inhibition of adipogenesis by Wnt signaling. Science. 2000; 289(5481):950-3. DOI: 10.1126/science.289.5481.950. View

14.

Heikkinen S, Auwerx J, Argmann C . PPARgamma in human and mouse physiology. Biochim Biophys Acta. 2007; 1771(8):999-1013. PMC: 2020525. DOI: 10.1016/j.bbalip.2007.03.006. View

15.

Kirkpatrick C, Mohr W, HAFERKAMP O . Lipid storage in cultured articular chondrocytes due to prostanoid precursors and a prostanoid synthesis inhibitor. Cell Tissue Res. 1982; 224(2):441-8. DOI: 10.1007/BF00216885. View

16.

Zhou H, Yang X, Wang N, Zhang Y, Cai G . Tigogenin inhibits adipocytic differentiation and induces osteoblastic differentiation in mouse bone marrow stromal cells. Mol Cell Endocrinol. 2007; 270(1-2):17-22. DOI: 10.1016/j.mce.2007.01.017. View

17.

Desvergne B, Wahli W . Peroxisome proliferator-activated receptors: nuclear control of metabolism. Endocr Rev. 1999; 20(5):649-88. DOI: 10.1210/edrv.20.5.0380. View

18.

Kulkarni N, Onyia J, Zeng Q, Tian X, Liu M, Halladay D . Orally bioavailable GSK-3alpha/beta dual inhibitor increases markers of cellular differentiation in vitro and bone mass in vivo. J Bone Miner Res. 2006; 21(6):910-20. DOI: 10.1359/jbmr.060316. View

19.

Akune T, Ohba S, Kamekura S, Yamaguchi M, Chung U, Kubota N . PPARgamma insufficiency enhances osteogenesis through osteoblast formation from bone marrow progenitors. J Clin Invest. 2004; 113(6):846-55. PMC: 362117. DOI: 10.1172/JCI19900. View

20.

Zhu Y, Qi C, Korenberg J, Chen X, Noya D, Rao M . Structural organization of mouse peroxisome proliferator-activated receptor gamma (mPPAR gamma) gene: alternative promoter use and different splicing yield two mPPAR gamma isoforms. Proc Natl Acad Sci U S A. 1995; 92(17):7921-5. PMC: 41258. DOI: 10.1073/pnas.92.17.7921. View