Original Article
You have full text access to this OnlineOpen article
Androgen receptor disruption increases the osteogenic response to mechanical loading in male mice
Article first published online: 14 DEC 2009
DOI: 10.1359/jbmr.091001
Copyright © 2010 American Society for Bone and Mineral Research
Additional Information
How to Cite
Callewaert, F., Bakker, A., Schrooten, J., Meerbeek, B. V., Verhoeven, G., Boonen, S. and Vanderschueren, D. (2010), Androgen receptor disruption increases the osteogenic response to mechanical loading in male mice. J Bone Miner Res, 25: 124–131. doi: 10.1359/jbmr.091001
Publication History
- Issue published online: 20 JAN 2010
- Article first published online: 14 DEC 2009
- Manuscript Accepted: 9 OCT 2009
- Manuscript Revised: 1 OCT 2009
- Manuscript Received: 3 AUG 2009
References
- 1, , , , . The diagnosis and treatment of male osteoporosis: defining, assessing, and preventing skeletal fragility in men. Eur J Intern Med. 2007; 18: 6–17.
- 2, , . Osteoporosis in men. Endocr Rev. 2008; 29: 441–464.
- 3. Periosteal bone formation: a neglected determinant of bone strength. N Engl J Med. 2003; 349: 320–323.
- 4. Bone's mechanostat: a 2003 update. Anat Rec A Discov Mol Cell Evol Biol. 2003; 275: 1081–1101.Direct Link:
- 5. Bone “mass” and the “mechanostat”: a proposal. Anat Rec. 1987; 219: 1–9.Direct Link:
- 6. Control of bone architecture by functional load bearing. J Bone Miner Res. 1992; 7: S369–375.Direct Link:
- 7, , , et al. The effect of mechanical loading on the size and shape of bone in pre-, peri-, and postpubertal girls: a study in tennis players. J Bone Miner Res. 2002; 17: 2274–2280.Direct Link:
- 8, , , , , . Cortical and trabecular bone mineral loss from the spine and hip in long-duration spaceflight. J Bone Miner Res. 2004; 19: 1006–1012.Direct Link:
- 9, , . Validation of a technique for studying functional adaptation of the mouse ulna in response to mechanical loading. Bone. 2002; 31: 407–412.
- 10, . Mechanical strain and bone cell function: a review. Osteoporos Int. 2002; 13: 688–700.
- 11, , . The role of osteocytes in bone mechanotransduction. Osteoporos Int. 2009; 20: 1686–1692.
- 12, . Osteocytes, mechanosensing and WNT signaling. Bone. 2008; 42: 606–615.
- 13, , , et al. Sensitivity of osteocytes to biomechanical stress in vitro. FASEB J. 1995; 9: 441–445.
- 14, , , et al. Targeted ablation of osteocytes induces osteoporosis with defective mechanotransduction. Cell Metab. 2007; 5: 464–475.
- 15, , , et al. Mechanical stimulation of bone in vivo reduces osteocyte expression of SOST/sclerostin. J Biol Chem. 2008; 283: 5866–5875.
- 16, , , , . Osteocyte-derived sclerostin inhibits bone formation: its role in bone morphogenetic protein and WNT signaling. J Bone Joint Surg. 2008; 90A: S31–35.
- 17, , , et al. Sclerostin is a delayed secreted product of osteocytes that inhibits bone formation. FASEB J. 2005; 19: 1842–1844.
- 18, , , . SOST/sclerostin, an osteocyte-derived negative regulator of bone formation. Cytokine Growth Factor Rev. 2005; 16: 319–327.
- 19, , , et al. Sclerostin mediates bone response to mechanical unloading via antagonizing WNT/beta-catenin signaling. J Bone Miner Res. 2009; 24: 1651–1661.Direct Link:
- 20, , , et al. WNT/beta-catenin signaling is a normal physiological response to mechanical loading in bone. J Biol Chem. 2006; 281: 31720–31728.
- 21, , , , , . Androgens and bone. Endocr Rev. 2004; 25: 389–425.
- 22, , , , . The “muscle-bone unit” during the pubertal growth spurt. Bone. 2004; 34: 771–775.
- 23, , , et al. Differential regulation of bone and body composition in male mice with combined inactivation of androgen and estrogen receptor-alpha. FASEB J. 2009; 23: 232–240.
- 24, , , , . Endocrinology: bone adaptation requires oestrogen receptor-alpha. Nature. 2003; 424: 389.
- 25, , , , . The adaptive response of bone to mechanical loading in female transgenic mice is deficient in the absence of oestrogen receptor-alpha and -beta. J Endocrinol. 2004; 182: 193–201.
- 26, , , et al. Osteoblast-like cells from estrogen receptor-alpha knockout mice have deficient responses to mechanical strain. J Bone Miner Res. 2004; 19: 938–946.Direct Link:
- 27, , , et al. A Sertoli cell-selective knockout of the androgen receptor causes spermatogenic arrest in meiosis. Proc Natl Acad Sci USA. 2004; 101: 1327–1332.
- 28, , , et al. Bone histomorphometry: standardization of nomenclature, symbols, and units. Report of the ASBMR Histomorphometry Nomenclature Committee. J Bone Miner Res. 1987; 2: 595–610.Direct Link:
- 29, , , , , . Analysis of nitrate, nitrite, and [15N]nitrate in biological fluids. Anal Biochem. 1982; 126: 131–138.
- 30, , . The effects of repetitive loading on bone mass and geometry in young male tennis players: a quantitative study using magnetic resonance imaging. J Bone Miner Res. 2009; 24: 1686–1692.Direct Link:
- 31, , , . Bone mass is preserved and cancellous architecture altered due to cyclic loading of the mouse tibia after orchidectomy. J Bone Miner Res. 2008; 23: 663–671.Direct Link:
- 32, , , et al. Relative impact of androgen and estrogen receptor activation in the effects of androgens on trabecular and cortical bone in growing male mice: a study in the androgen receptor knockout mouse model. J Bone Miner Res. 2006; 21: 576–585.Direct Link:
- 33, , , , , . The contribution of testosterone to skeletal development and maintenance: lessons from the androgen insensitivity syndrome. J Clin Endocrinol Metab. 2000; 85: 1032–1037.
- 34, , , et al. Testosterone dose-response relationships in healthy young men. Am J Physiol Endocrinol Metab. 2001; 281: E1172–1181.
- 35, . Estrogen receptor beta: the antimechanostat? Bone. 2005; 36: 185–192.
- 36, , , , . The skeletal responsiveness to mechanical loading is enhanced in mice with a null mutation in estrogen receptor-beta. Am J Physiol Endocrinol Metab. 2007; 293: E484–491.
- 37, , , et al. Serum estradiol is associated with volumetric BMD and modulates the impact of physical activity on bone size at the age of peak bone mass: a study in healthy male siblings. J Bone Miner Res. 2009; 24: 1075–1085.Direct Link:
- 38, , , et al. WNT/beta-catenin signaling is a component of osteoblastic bone cell early responses to load-bearing and requires estrogen receptor-alpha. J Biol Chem. 2007; 282: 20715–20727.
- 39, , . Quantifying the strain history of bone: spatial uniformity and self-similarity of low-magnitude strains. J Biomech. 2000; 33: 317–325.
- 40, , . A model for the excitation of osteocytes by mechanical loading-induced bone fluid shear stresses. J Biomech. 1994; 27: 339–360.
- 41, , . Nitric oxide is an early mediator of the increase in bone formation by mechanical stimulation. Am J Physiol. 1996; 270: E955–960.
- 42. Inducible cyclooxygenase (COX-2) mediates the induction of bone formation by mechanical loading in vivo. J Bone Miner Res. 1996; 11: 1688–1693.Direct Link:
- 43, , , , . Pulsating fluid flow stimulates prostaglandin release and inducible prostaglandin G/H synthase mRNA expression in primary mouse bone cells. J Bone Miner Res. 1997; 12: 45–51.Direct Link:
- 44, . Nitric oxide and bone. Immunology. 2001; 103: 255–261.Direct Link:
- 45, , , , . Pulsating fluid flow increases nitric oxide (NO) synthesis by osteocytes but not periosteal fibroblasts: correlation with prostaglandin upregulation. Biochem Biophys Res Commun. 1995; 217: 640–648.
- 46, , , , , . Mechanical strain-induced NO production by bone cells: a possible role in adaptive bone (re)modeling? FASEB J. 1995; 9: 1614–1622.
- 47, , , . Role of nitric oxide and prostaglandins in mechanically induced bone formation. J Bone Miner Res. 1998; 13: 1039–1044.Direct Link:
- 48, , . Prostaglandin endoperoxide H synthases (cyclooxygenases)-1 and -2. J Biol Chem. 1996; 271: 33157–33160.
- 49, , . Mechanotransduction in bone cells proceeds via activation of COX-2, but not COX-1. Biochem Biophys Res Commun. 2003; 305: 677–683.

1523-4681/asset/olbannerleft.gif?v=1&s=d7e4c0e37904a489128d3a4e58ba94214db307a9)
1523-4681/asset/olbannerright.gif?v=1&s=854ee0e4d351ead9faaca8bfab3e50b1c7c9d03d)
