In vivo live imaging of bone cells
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There are as many as 200 cell types in the body, and highly sophisticated and varied life phenomena are carried out by cell migration to appropriate places at appropriate times following the appropriate interactions. Recent advances in optical imaging technology using multi-photon excitation microscopy have enabled visualization inside intact bone tissues in living animals without thin sectioning. Using such advanced techniques, the dynamic behaviors of living bone cells on intact bone tissue structures can be elucidated. Here, we focus on recent findings using intravital multi-photon imaging of dynamic biological systems, e.g., bone homeostasis. This novel approach has proven beneficial for understanding the mechanisms underlying the spatiotemporal nature of bone remodeling systems and for evaluating the specific modes of actions of novel drugs currently in development, which will contribute to a new chapter in bone and mineral research.
KeywordsIntravital imaging Multi-photon microscopy Cellular dynamics Bone Osteoclast pH probe
This work was supported by CREST, Japan Science and Technology Agency, and Grants-in-Aid for Scientific Research (A) from the Japan Society for the Promotion of Science (JSPS to M.I.); Grant-in-Aid for Young Scientists (A) from JSPS (to J.K.); and Grant-in-Aid for Young Scientists (B) from JSPS (to H.M.).
- Kikuta J, Kawamura S, Okiji F, Shirazaki M, Sakai S, Saito H, Ishii M (2013a) Sphingosine-1-phosphate-mediated osteoclast precursor monocyte migration is a critical point of control in antibone-resorptive action of active vitamin D. Proc Natl Acad Sci USA 110:7009–7013. https://doi.org/10.1073/pnas.1218799110 CrossRefPubMedPubMedCentralGoogle Scholar
- Kikuta J, Wada Y, Kowada T, Wang Z, Sun-Wada GH, Nishiyama I, Mizukami S, Maiya N, Yasuda H, Kumanogoh A, Kikuchi K, Germain RN, Ishii M (2013b) Dynamic visualization of RANKL and Th17-mediated osteoclast function. J Clin Invest 123(2):866–873. https://doi.org/10.1172/JCI65054 PubMedPubMedCentralGoogle Scholar
- Nakashima T, Hayashi M, Fukunaga T, Kurata K, Oh-Hora M, Feng JQ, Bonewald LF, Kodama T, Wutz A, Wagner EF, Penninger JM, Takayanagi H (2011) Evidence for osteocyte regulation of bone homeostasis through RANKL expression. Nat Med 17:1231–1234. https://doi.org/10.1038/nm.2452 CrossRefPubMedGoogle Scholar
- Ohba S, Ikeda T, Kugimiya F, Yano F, Lichtler AC, Nakamura K, Takato T, Kawaguchi H, Chung UI (2007) Identification of a potent combination of osteogenic genes for bone regeneration using embryonic stem (ES) cell-based sensor. FASEB J 21:1777–1787. https://doi.org/10.1096/fj.06-7571com CrossRefPubMedGoogle Scholar
- Sakaue-Sawano A, Kurokawa H, Morimura T, Hanyu A, Hama H, Osawa H, Kashiwagi S, Fukami K, Miyata T, Miyoshi H, Imamura T, Ogawa M, Masai H, Miyawaki A (2008) Visualizing spatiotemporal dynamics of multicellular cell-cycle progression. Cell 132:487–498. https://doi.org/10.1016/j.cell.2007.12.033 CrossRefPubMedGoogle Scholar