R-spondin 1 promotes vibration-induced bone formation in mouse models of osteoporosis

Haitao Wang, Tracy A. Brennan, Elizabeth Russell, Jung Hoon Kim, Kevin P. Egan, Qijun Chen, Craig Israelite, David C. Schultz, Frederick B. Johnson, Robert J. Pignolo

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

Bone tissue adapts to its functional environment by optimizing its morphology for mechanical demand. Among the mechanosensitive cells that recognize and respond to forces in the skeleton are osteocytes, osteoblasts, and mesenchymal progenitor cells (MPCs). Therefore, the ability to use mechanical signals to improve bone health through exercise and devices that deliver mechanical signals is an attractive approach to age-related bone loss; however, the extracellular or circulating mediators of such signals are largely unknown. Using SDS-PAGE separation of proteins secreted by MPCs in response to low-magnitude mechanical signals and in-gel trypsin digestion followed by HPLC and mass spectroscopy, we identified secreted proteins up-regulated by vibratory stimulation. We exploited a cell senescence-associated secretory phenotype screen and reasoned that a subset of vibration-induced proteins with diminished secretion by senescent MPCs will have the capacity to promote bone formation in vivo. We identified one such vibration-induced bone-enhancing (vibe) gene as R-spondin 1, a Wnt pathway modulator, and demonstrated that it has the capacity to promote bone formation in three mouse models of age-related bone loss. By virtue of their secretory status, some vibe proteins may be candidates for pre-clinical development as anabolic agents for the treatment of osteoporosis. Key message: Mesenchymal stem cells respond to low magnitude mechanical signals (vibration). R-Spondin 1 is upregulated by mechanical signals and secreted. R-Spondin 1 promotes bone formation in three mouse models of osteoporosis.

Original languageEnglish (US)
Pages (from-to)1421-1429
Number of pages9
JournalJournal of Molecular Medicine
Volume91
Issue number12
DOIs
StatePublished - Dec 2013

Keywords

  • Aging
  • Mechanical signals
  • Mesenchymal stem cells
  • Osteoporosis
  • R-spondin 1
  • Telomerase
  • Telomere
  • Vibration

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery
  • Genetics(clinical)

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    Wang, H., Brennan, T. A., Russell, E., Kim, J. H., Egan, K. P., Chen, Q., Israelite, C., Schultz, D. C., Johnson, F. B., & Pignolo, R. J. (2013). R-spondin 1 promotes vibration-induced bone formation in mouse models of osteoporosis. Journal of Molecular Medicine, 91(12), 1421-1429. https://doi.org/10.1007/s00109-013-1068-3