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Osteopontin Facilitates Bone Resorption, Decreasing Bone Mineral Crystallinity and Content During Calcium Deficiency

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Abstract

Osteopontin null-mice were previously shown to have bones containing more mineral and larger mineral crystals. These bones were independently seen to be resistant to ovariectomy-induced remodeling. To separate the physicochemical effects of osteopontin, which is an in vitro inhibitor of mineral crystal formation and growth, from effects of osteopontin on in vivo bone remodeling, this study examined mature (5-month-old) osteopontin-null (Opn−/−) and wildtype (WT) mice given a calcium-deficient diet. Biochemical parameters were measured during 4 weeks of Ca deficiency, followed by 1 week of refeeding adequate Ca. Ca deficiency caused a transiently greater rise in bone resorption in WT than Opn−/− mice (P = 0.01), whereas only the Opn−/− mice tended to increase Ca absorption (P = 0.08), yet both groups showed elevated levels of parathyroid hormone (PTH) (P < 0.001). The rise in markers of bone formation due to Ca deficiency was similar in both groups during Ca deficiency. Fourier transform infrared microspectroscopy assessed mineral properties at 20 µm spatial resolution in different anatomic regions of the bone. The Ca-deficient Opn−/− animals had slightly increased mineral content as compared to the WT, and there was a significant increase in the mineral content of older (endosteal) bone, implying that osteoclast recruitment was impaired. Crystallinity in the Ca-deficient Opn−/− bones was increased relative to the Ca-deficient WT at all sites except adjacent to the periosteum (younger mineral). These data suggest that osteopontin has both a physicochemical effect (inhibiting crystal growth and crystal proliferation) and a role in osteoclast recruitment, and in its absence, extraskeletal organs maintain calcium homeostasis.

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Acknowledgements

This work was supported by NIH grants DE04141 (Boskey), AR44434 (Denhardt) and AG12161 (Shapses). The authors would like to thank Ms Orla O’Shea for her assistance with this project.

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Authors and Affiliations

  1. Department of Nutritional Sciences, Rutgers University, New Brunswick, NJ, USA

    S. A. Shapses, M. Cifuentes & H. Chowdhury

  2. Mineralized Tissues Laboratory, Hospital for Special Surgery, New York, NY 10021, USA

    L. Spevak & A. L. Boskey

  3. Department of Cell Biology and Neuroscience, Rutgers University, Piscataway, NJ, USA

    J. Brittingham & D. T. Denhardt

Authors
  1. S. A. Shapses
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  2. M. Cifuentes
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  3. L. Spevak
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  4. H. Chowdhury
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  5. J. Brittingham
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  6. A. L. Boskey
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  7. D. T. Denhardt
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Corresponding author

Correspondence to A. L. Boskey.

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Shapses, S., Cifuentes, M., Spevak, L. et al. Osteopontin Facilitates Bone Resorption, Decreasing Bone Mineral Crystallinity and Content During Calcium Deficiency . Calcif Tissue Int 73, 86–92 (2003). https://doi.org/10.1007/s00223-002-1090-x

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