Original Article

You have full text access to this OnlineOpen article

The orphan nuclear receptor SHP is a positive regulator of osteoblastic bone formation

  1. Byung-Chul Jeong1,
  2. Yong-Soo Lee2,
  3. In-Ho Bae1,
  4. Chul-Ho Lee3,
  5. Hong-In Shin4,
  6. Hyun Jung Ha5,
  7. Renny T Franceschi6,
  8. Hueng-Sik Choi2,*,
  9. Jeong-Tae Koh1,*

Article first published online: 14 DEC 2009

DOI: 10.1359/jbmr.090718

Issue

Journal of Bone and Mineral Research

Journal of Bone and Mineral Research

Volume 25, Issue 2, pages 262–274, February 2010

Additional Information

How to Cite

Jeong, B.-C., Lee, Y.-S., Bae, I.-H., Lee, C.-H., Shin, H.-I., Ha, H. J., Franceschi, R. T., Choi, H.-S. and Koh, J.-T. (2010), The orphan nuclear receptor SHP is a positive regulator of osteoblastic bone formation. J Bone Miner Res, 25: 262–274. doi: 10.1359/jbmr.090718

Author Information

  1. 1

    Dental Science Research Institute, School of Dentistry, Chonnam National University, Gwangju, Republic of Korea

  2. 2

    Hormone Research Center, School of Biological Sciences and Technology, Chonnam National University, Gwangju, Republic of Korea

  3. 3

    Korea Research Institute of Bioscience and Biotechnology, Daejeon, Republic of Korea

  4. 4

    Department of Oral Pathology and IHBR, School of Dentistry, Kyungpook National University, Daegu, Republic of Korea

  5. 5

    Department of Biochemistry, Biotechnology Research Institute, School of Life Sciences, Chungbuk National University, Cheongju, Republic of Korea

  6. 6

    Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, Ann Arbor, MI, USA

*Hormone Research Center, Chonnam National University, Gwangju, 500-757, Republic of Korea.

Publication History

  1. Issue published online: 19 FEB 2010
  2. Article first published online: 14 DEC 2009
  3. Manuscript Accepted: 6 JUL 2009
  4. Manuscript Revised: 27 MAY 2009
  5. Manuscript Received: 8 DEC 2008

SEARCH

SEARCH BY CITATION

ARTICLE TOOLS

View Full Article (HTML) Get PDF (545K)

References

  • 1
    Seol W, Choi HS, Moore DD. An orphan nuclear hormone receptor that lacks a DNA binding domain and heterodimerizes with other receptors. Science. 1996; 272: 1336–1339.
  • 2
    Lee YS, Chanda D, Sim J, Park YY, Choi HS. Structure and function of the atypical orphan nuclear receptor small heterodimer partner. Int Rev Cytol. 2007; 261: 117–158.
  • 3
    Chanda D, Park JH, Choi HS. Molecular basis of endocrine regulation by orphan nuclear receptor small heterodimer partner. Endocr J. 2008; 55: 253–268.
  • 4
    Kim YD, Park KG, Lee YS, et al. Metformin inhibits hepatic gluconeogenesis through AMP-activated protein kinase-dependent regulation of the orphan nuclear receptor SHP. Diabetes. 2008; 57: 306–314.
  • 5
    Huang J, Iqbal J, Saha PK, et al. Molecular characterization of the role of orphan receptor small heterodimer partner in development of fatty liver. Hepatology. 2007; 46: 147–157.
  • 6
    Park KG, Lee KM, Seo HY, et al. Glucotoxicity in the INS-1 rat insulinoma cell line is mediated by the orphan nuclear receptor small heterodimer partner. Diabetes. 2007; 56: 431–437.
  • 7
    Song KH, Ellis E, Strom S, Chiang JY. Hepatocyte growth factor signaling pathway inhibits cholesterol 7α-hydroxylase and bile acid synthesis in human hepatocytes. Hepatology. 2007; 46: 1993–2002.
  • 8
    Olsen BR, Reginato AM, Wang W. Bone development. Annu Rev Cell Dev Biol. 2000; 16: 191–220.
  • 9
    Pittenger MF, Mackay AM, Beck SC, et al. Multilineage potential of adult human mesenchymal stem cells. Science. 1999; 284: 143–147.
  • 10
    Yamaguchi A, Komori T, Suda T. Regulation of osteoblast differentiation mediated by bone morphogenetic proteins, hedgehogs, and Cbfa1. Endocr Rev. 2000; 21: 393–411.
  • 11
    Komori T. Regulation of osteoblast differentiation by transcription factors. J Cell Biochem. 2006; 99: 1233–1239.
  • 12
    Wozney JM, Rosen V, Celeste AJ, et al. Novel regulators of bone formation: molecular clones and activities. Science. 1988; 242: 1528–1534.
  • 13
    Franceschi RT, Ge C, Xiao G, Roca H, Jiang D. Transcriptional regulation of osteoblasts. Ann NY Acad Sci. 2007; 1116: 196–207.
  • 14
    Komori T. Regulation of skeletal development by the Runx family of transcription factors. J Cell Biochem. 2005; 95: 445–453.
  • 15
    Banerjee C, McCabe LR, Choi JY, et al. Runt homology domain proteins in osteoblast differentiation: AML3/CBFA1 is a major component of a bone-specific complex. J Cell Biochem. 1997; 66: 1–8.
  • 16
    Ducy P, Zhang R, Geoffroy V, Ridall AL, Karsenty G. Osf2/Cbfa1: a transcriptional activator of osteoblast differentiation. Cell. 1997; 89: 747–754.
  • 17
    Harada H, Tagashira S, Fujiwara M, et al. Cbfa1 isoforms exert functional differences in osteoblast differentiation. J Biol Chem. 1999; 274: 6972–6978.
  • 18
    Lee KS, Kim HJ, Li QL, et al. Runx2 is a common target of transforming growth factor β1 and bone morphogenetic protein 2, and cooperation between Runx2 and Smad5 induces osteoblast-specific gene expression in the pluripotent mesenchymal precursor cell line C2C12. Mol Cell Biol. 2000; 20: 8783–8792.
  • 19
    Sierra J, Villagra A, Paredes R, et al. Regulation of the bone-specific osteocalcin gene by p300 requires Runx2/Cbfa1 and the vitamin D3 receptor but not p300 intrinsic histone acetyltransferase activity. Mol Cell Biol. 2003; 23: 3339–3351.
  • 20
    McLarren KW, Lo R, Grbavec D, Thirunavukkarasu K, Karsenty G, Stifani S. The mammalian basic helix loop helix protein HES-1 binds to and modulates the transactivating function of the runt-related factor Cbfa1. J Biol Chem. 2000; 275: 530–538.
  • 21
    Yagi R, Chen LF, Shigesada K, Murakami Y, Ito Y. A WW domain-containing yes-associated protein (YAP) is a novel transcriptional co-activator. EMBO J. 1999; 18: 2551–2562.
  • 22
    Westendorf JJ. Transcriptional co-repressors of Runx2. J Cell Biochem. 2006; 98: 54–64.
  • 23
    Takai H, Nakayama Y, Kim DS, et al. Androgen receptor stimulates bone sialoprotein (BSP) gene transcription via cAMP response element and activator protein 1/glucocorticoid response elements. J Cell Biochem. 2007; 102: 240–251.
  • 24
    Nakamura T, Imai Y, Matsumoto T, et al. Estrogen prevents bone loss via estrogen receptor α and induction of Fas ligand in osteoclasts. Cell. 2007; 130: 811–823.
  • 25
    Zirngibl RA, Chan JS, Aubin JE. Estrogen receptor-related receptor α (ERRα) regulates osteopontin expression through a non-canonical ERRα response element in a cell context-dependent manner. J Mol Endocrinol. 2008; 40: 61–73.
  • 26
    Lee HK, Lee YK, Park SH, et al. Structure and expression of the orphan nuclear receptor SHP gene. J Biol Chem. 1998; 273: 14398–14402.
  • 27
    Kim JY, Kim HJ, Kim KT, et al. Orphan nuclear receptor small heterodimer partner represses hepatocyte nuclear factor 3/Foxa transactivation via inhibition of its DNA binding. Mol Endocrinol. 2004; 18: 2880–2894.
  • 28
    Lee YS, Kim DK, Kim YD, et al. Orphan nuclear receptor SHP interacts with and represses hepatocyte nuclear factor-6 (HNF-6) transactivation. Biochem J. 2008; 413: 559–569.
  • 29
    Phimphilai M, Zhao Z, Boules H, Roca H, Franceschi RT. BMP signaling is required for RUNX2-dependent induction of the osteoblast phenotype. J Bone Miner Res. 2006; 21: 637–646.
  • 30
    Ichida F, Nishimura R, Hata K, et al. Reciprocal roles of MSX2 in regulation of osteoblast and adipocyte differentiation. J Biol Chem. 2004; 279: 34015–34022.
  • 31
    Manolagas SC, Burton DW, Deftos LJ. 1,25-Dihydroxyvitamin D3 stimulates the alkaline phosphatase activity of osteoblast-like cells. J Biol Chem. 1981; 256: 7115–7117.
  • 32
    Kim H, Choi HK, Shin JH, et al. Selective inhibition of RANK blocks osteoclast maturation and function and prevents bone loss in mice. J Clin Invest. 2009; 119: 813–825.
  • 33
    Park YJ, Qatanani M, Chua SS, et al. Loss of orphan receptor small heterodimer partner sensitizes mice to liver injury from obstructive cholestasis. Hepatology. 2008; 47: 1578–1586.
  • 34
    Ahrens M, Ankenbauer T, Schroder D, Hollnagel A, Mayer H, Gross G. Expression of human bone morphogenetic proteins-2 or -4 in murine mesenchymal progenitor C3H10T1/2 cells induces differentiation into distinct mesenchymal cell lineages. DNA Cell Biol. 1993; 12: 871–880.
  • 35
    Chen Y, Bhushan A, Vale W. Smad8 mediates the signaling of the ALK-2 [corrected] receptor serine kinase. Proc Natl Acad Sci USA. 1997; 94: 12938–12943.
  • 36
    Takuwa Y, Ohse C, Wang EA, Wozney JM, Yamashita K. Bone morphogenetic protein-2 stimulates alkaline phosphatase activity and collagen synthesis in cultured osteoblastic cells, MC3T3-E1. Biochem Biophys Res Commun. 1991; 174: 96–101.
  • 37
    Puleo DA. Dependence of mesenchymal cell responses on duration of exposure to bone morphogenetic protein-2 in vitro. J Cell Physiol. 1997; 173: 93–101.
  • 38
    Khosla S, Westendorf JJ, Oursler MJ. Building bone to reverse osteoporosis and repair fractures. J Clin Invest. 2008; 118: 421–428.
  • 39
    Makita N, Suzuki M, Asami S, et al. Two of four alternatively spliced isoforms of RUNX2 control osteocalcin gene expression in human osteoblast cells. Gene. 2008; 413: 8–17.
  • 40
    Vega RB, Matsuda K, Oh J, et al. Histone deacetylase 4 controls chondrocyte hypertrophy during skeletogenesis. Cell. 2004; 119: 555–566.
  • 41
    Tsuji K, Bandyopadhyay A, Harfe BD, et al. BMP-2 activity, although dispensable for bone formation, is required for the initiation of fracture healing. Nat Genet. 2006; 38: 1424–1429.
  • 42
    Harada S, Rodan GA. Control of osteoblast function and regulation of bone mass. Nature. 2003; 423: 349–355.
  • 43
    Teitelbaum SL, Ross FP. Genetic regulation of osteoclast development and function. Nat Rev Genet. 2003; 4: 638–649.
  • 44
    Kassam A, Capone JP, Rachubinski RA. The short heterodimer partner receptor differentially modulates peroxisome proliferator-activated receptor alpha-mediated transcription from the peroxisome proliferator-response elements of the genes encoding the peroxisomal beta-oxidation enzymes acyl-CoA oxidase and hydratase-dehydrogenase. Mol Cell Endocrinol. 2001; 176: 49–56.
  • 45
    Nishizawa H, Yamagata K, Shimomura I, et al. Small heterodimer partner, an orphan nuclear receptor, augments peroxisome proliferator-activated receptor gamma transactivation. J Biol Chem. 2002; 277: 1586–1592.
  • 46
    Park MJ, Kim KH, Kim HY, Kim K, Cheong J. Bile acid induces expression of COX-2 through the homeodomain transcription factor CDX1 and orphan nuclear receptor SHP in human gastric cancer cells. Carcinogenesis. 2008; 29: 2385–2393.
  • 47
    Erlebacher A, Filvaroff EH, Gitelman SE, Derynck R. Toward a molecular understanding of skeletal development. Cell. 1995; 80: 371–378.
  • 48
    Farhana L, Dawson MI, Leid M, et al. Adamantyl-substituted retinoid-related molecules bind small heterodimer partner and modulate the Sin3A repressor. Cancer Res. 2007; 67: 318–325.
View Full Article (HTML) Get PDF (545K)