Original Article

You have full text access to this OnlineOpen article

Overexpression of secreted frizzled-related protein 1 inhibits bone formation and attenuates parathyroid hormone bone anabolic effects

  1. Wei Yao1,*,
  2. Zhiqiang Cheng1,
  3. Mohammad Shahnazari1,
  4. Wewei Dai1,
  5. Mark L Johnson2,
  6. Nancy E Lane1

Article first published online: 14 DEC 2009

DOI: 10.1359/jbmr.090719

Issue

Journal of Bone and Mineral Research

Journal of Bone and Mineral Research

Volume 25, Issue 2, pages 190–199, February 2010

Additional Information

How to Cite

Yao, W., Cheng, Z., Shahnazari, M., Dai, W., Johnson, M. L. and Lane, N. E. (2010), Overexpression of secreted frizzled-related protein 1 inhibits bone formation and attenuates parathyroid hormone bone anabolic effects. Journal of Bone and Mineral Research, 25: 190–199. doi: 10.1359/jbmr.090719

Author Information

  1. 1

    Department of Medicine, UC Davis Medical Center, Sacramento, CA, USA

  2. 2

    Department of Oral Biology, UMKC School of Dentistry, Kansas City, MO, USA

*Department of Medicine, University of California at Davis Medical Center, Sacramento, CA 94110, USA.

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: 4 MAY 2009
  5. Manuscript Received: 2 FEB 2009

SEARCH

SEARCH BY CITATION

ARTICLE TOOLS

View Full Article (HTML) Get PDF (280K)

References

  • 1
    Fuerer C, Nusse R, Ten Berge D. Wnt signalling in development and disease. Max Delbruck Center for Molecular Medicine Meeting on Wnt Signaling in Development and Disease. EMBO Rep. 2008; 9: 134–138.
  • 2
    Gong Y, Slee RB, Fukai N, et al. LDL receptor-related protein 5 (LRP5) affects bone accrual and eye development. Cell. 2001; 107: 513–523.
  • 3
    Little RD, Carulli JP, Del Mastro RG, et al. A mutation in the LDL receptor-related protein 5 gene results in the autosomal dominant high-bone-mass trait. Am J Hum Genet. 2002; 70: 11–19.
  • 4
    Bennett CN, Longo KA, Wright WS, et al. Regulation of osteoblastogenesis and bone mass by Wnt10b. Proc Natl Acad Sci USA. 2005; 102: 3324–3329.
  • 5
    Andrade AC, Nilsson O, Barnes KM, Baron J. Wnt gene expression in the post-natal growth plate: regulation with chondrocyte differentiation. Bone. 2007; 40: 1361–1369.
  • 6
    Rodda SJ, McMahon AP. Distinct roles for Hedgehog and canonical Wnt signaling in specification, differentiation and maintenance of osteoblast progenitors. Development. 2006; 133: 3231–3244.
  • 7
    Dong YF, Soung Do Y, Schwarz EM, O'Keefe RJ, Drissi H. Wnt induction of chondrocyte hypertrophy through the Runx2 transcription factor. J Cell Physiol. 2006; 208: 77–86.
  • 8
    Glass DA 2nd, Bialek P, Ahn JD, et al. Canonical Wnt signaling in differentiated osteoblasts controls osteoclast differentiation. Dev Cell. 2005; 8: 751–764.
  • 9
    Bovolenta P, Esteve P, Ruiz JM, Cisneros E, Lopez-Rios J. Beyond Wnt inhibition: new functions of secreted frizzled-related proteins in development and disease. J Cell Sci. 2008; 121: 737–746.
  • 10
    Bodine PV, Billiard J, Moran RA, et al. The Wnt antagonist secreted frizzled-related protein-1 controls osteoblast and osteocyte apoptosis. J Cell Biochem. 2005; 96: 1212–1230.
  • 11
    Bodine PV, Zhao W, Kharode YP, et al. The Wnt antagonist secreted frizzled-related protein-1 is a negative regulator of trabecular bone formation in adult mice. Mol Endocrinol. 2004; 18: 1222–1237.
  • 12
    Bodine PV, Seestaller-Wehr L, Kharode YP, Bex FJ, Komm BS. Bone anabolic effects of parathyroid hormone are blunted by deletion of the Wnt antagonist secreted frizzled-related protein-1. J Cell Physiol. 2007; 210: 352–357.
  • 13
    Hausler KD, Horwood NJ, Chuman Y, et al. Secreted frizzled-related protein-1 inhibits RANKL-dependent osteoclast formation. J Bone Miner Res. 2004; 19: 1873–1881.
  • 14
    Liu D, Wise GE. A DNA microarray analysis of chemokine and receptor genes in the rat dental follicle: role of secreted frizzled-related protein-1 in osteoclastogenesis. Bone. 2007; 41: 266–272.
  • 15
    Bodine P, Stauffer B, Ponce-de-Leon H, Bhat B, Mangine A, Seestaller-Wehr L. A small molecule inhibitor of the Wnt antagonist secreted frizzled-related protein (SFRP)-1 stimulates bone formation. J Bone Miner Res. 2007; 22: S4.
  • 16
    Gong S, Yang XW, Li C, Heintz N. Highly efficient modification of bacterial artificial chromosomes (BACs) using novel shuttle vectors containing the R6Kγ origin of replication. Genome Res. 2002; 12: 1992–1998 .
  • 17
    Lane NE, Yao W, Balooch M, et al. Glucocorticoid-treated mice have localized changes in trabecular bone material properties and osteocyte lacunar size that are not observed in placebo-treated or estrogen-deficient mice. J Bone Miner Res. 2006; 21: 466–476.
  • 18
    Yao W, Cheng Z, Busse C, Pham A, Nakamura MC, Lane NE. Glucocorticoid excess in mice results in early activation of osteoclastogenesis and adipogenesis and prolonged suppression of osteogenesis: a longitudinal study of gene expression in bone tissue from glucocorticoid-treated mice. Arthritis Rheum. 2008; 58: 1674–1686.
  • 19
    Yao W, Cheng Z, Pham A, et al. Glucocorticoid-induced bone loss in mice can be reversed by the actions of parathyroid hormone and risedronate on different pathways for bone formation and mineralization. Arthritis Rheum. 2008; 58: 3485–3497.
  • 20
    Holmen SL, Zylstra CR, Mukherjee A, et al. Essential role of beta-catenin in postnatal bone acquisition. J Biol Chem. 2005; 280: 21162–21168.
  • 21
    Boyce BF, Xing L, Chen D. Osteoprotegerin, the bone protector, is a surprising target for beta-catenin signaling. Cell Metab. 2005; 2: 344–345.
  • 22
    Goldring SR, Goldring MB. Eating bone or adding it: the Wnt pathway decides. Nat Med. 2007; 13: 133–134.
  • 23
    Diarra D, Stolina M, Polzer K, et al. Dickkopf-1 is a master regulator of joint remodeling. Nat Med. 2007; 13: 156–163.
  • 24
    Huang JC, Sakata T, Pfleger LL, et al. PTH differentially regulates expression of RANKL and OPG. J Bone Miner Res. 2004; 19: 235–244.
  • 25
    Ferrari SL, Deutsch S, Baudoin C, et al. LRP5 gene polymorphisms and idiopathic osteoporosis in men. Bone. 2005; 37: 770–775.
  • 26
    Ferrari SL, Deutsch S, Choudhury U, et al. Polymorphisms in the low-density lipoprotein receptor-related protein 5 (LRP5) gene are associated with variation in vertebral bone mass, vertebral bone size, and stature in whites. Am J Hum Genet. 2004; 74: 866–875.
  • 27
    Kiel DP, Ferrari SL, Cupples LA, et al. Genetic variation at the low-density lipoprotein receptor-related protein 5 (LRP5) locus modulates Wnt signaling and the relationship of physical activity with bone mineral density in men. Bone. 2007; 40: 587–596.
  • 28
    van Meurs JB, Trikalinos TA, Ralston SH, et al. Large-scale analysis of association between LRP5 and LRP6 variants and osteoporosis. JAMA. 2008; 299: 1277–1290.
  • 29
    Sawakami K, Robling AG, Ai M, et al. The Wnt co-receptor LRP5 is essential for skeletal mechanotransduction but not for the anabolic bone response to parathyroid hormone treatment. J Biol Chem. 2006; 281: 23698–23711.
  • 30
    Akhter MP, Wells DJ, Short SJ, et al. Bone biomechanical properties in LRP5 mutant mice. Bone. 2004; 35: 162–169.
  • 31
    Babij P, Zhao W, Small C, et al. High bone mass in mice expressing a mutant LRP5 gene. J Bone Miner Res. 2003; 18: 960–974.
  • 32
    Zhang Y, Wang Y, Li X, et al. The LRP5 high-bone-mass G171V mutation disrupts LRP5 interaction with Mesd. Mol Cell Biol. 2004; 24: 4677–4684.
  • 33
    Hock JM. Anabolic actions of PTH in the skeletons of animals. J Musculoskelet Neuronal Interact. 2001; 2: 33–47.
  • 34
    Bringhurst FR. PTH receptors and apoptosis in osteocytes. J Musculoskelet Neuronal Interact. 2002; 2: 245–251.
  • 35
    Turner PR, Mefford S, Christakos S, Nissenson RA. Apoptosis mediated by activation of the G protein-coupled receptor for parathyroid hormone (PTH)/PTH-related protein (PTHrP). Mol Endocrinol. 2000; 14: 241–254.
  • 36
    Karaplis AC, Deckelbaum RA. Role of PTHrP and PTH-1 receptor in endochondral bone development. Front Biosci. 1998; 3: d795–d803.
  • 37
    Kulkarni NH, Halladay DL, Miles RR, et al. Effects of parathyroid hormone on Wnt signaling pathway in bone. J Cell Biochem. 2005; 95: 1178–1190.
  • 38
    Tobimatsu T, Kaji H, Sowa H, et al. Parathyroid hormone increases beta-catenin levels through Smad3 in mouse osteoblastic cells. Endocrinology. 2006; 147: 2583–2590.
  • 39
    Bellido T. Downregulation of SOST/sclerostin by PTH: a novel mechanism of hormonal control of bone formation mediated by osteocytes. J Musculoskel Neuronal Interact. 2006; 6: 358–359.
  • 40
    Keller H, Kneissel M. SOST is a target gene for PTH in bone. Bone. 2005; 37: 148–158.
  • 41
    O'Brien CA, Plotkin LI, Galli C, et al. Control of bone mass and remodeling by PTH receptor signaling in osteocytes. PLoS ONE. 2008; 3: e2942.
  • 42
    Iwaniec UT, Wronski TJ, Liu J, et al. PTH stimulates bone formation in mice deficient in Lrp5. J Bone Miner Res. 2007; 22: 394–402.
  • 43
    Wan M, Yang C, Li J, et al. Parathyroid hormone signaling through low-density lipoprotein-related protein 6. Genes Dev. 2008; 22: 2968–2979.
  • 44
    Gallagher JC. Advances in bone biology and new treatments for bone loss. Maturitas. 2008; 60: 65–69.
  • 45
    Simonet WS, Lacey DL, Dunstan CR, et al. Osteoprotegerin: a novel secreted protein involved in the regulation of bone density. Cell. 1997; 89: 309–319.
  • 46
    Yadav VK, Ryu JH, Suda N, et al. Lrp5 controls bone formation by inhibiting serotonin synthesis in the duodenum. Cell. 2008; 135: 825–837.
View Full Article (HTML) Get PDF (280K)