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dc.contributor.authorCooper, Kimberly L.en_US
dc.contributor.authorOh, Seungeunen_US
dc.contributor.authorSung, Yongjinen_US
dc.contributor.authorDasari, Ramachandra R.en_US
dc.contributor.authorKirschner, Marc W.en_US
dc.contributor.authorTabin, Clifford J.en_US
dc.date.accessioned2014-03-10T16:17:46Z
dc.date.issued2013en_US
dc.identifier.citationCooper, Kimberly L., Seungeun Oh, Yongjin Sung, Ramachandra R. Dasari, Marc W. Kirschner, and Clifford J. Tabin. 2013. “Multiple Phases of Chondrocyte Enlargement Underlie Differences in Skeletal Proportions.” Nature 495 (7441): 375-378. doi:10.1038/nature11940. http://dx.doi.org/10.1038/nature11940.en
dc.identifier.issn0028-0836en
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:11877135
dc.description.abstractEven a casual pass through the great halls of mammals in the world’s natural history museums highlights the wide diversity of skeletal proportions that allow us to distinguish between species even when reduced to their calcified components. Similarly each individual is comprised of a variety of bones of differing lengths. The largest contribution to the lengthening of a skeletal element, and to the differential elongation of elements, comes from a dramatic increase in the volume of hypertrophic chondrocytes in the growth plate as they undergo terminal differentiation1–7. Despite this recognized importance, the mechanisms of chondrocyte volume enlargement have remained a mystery8–11. Here we use quantitative phase microscopy12 to show that chondrocytes undergo three distinct phases of volume increase, including a phase of massive cell swelling in which the cellular dry mass is significantly diluted. In light of the tight fluid regulatory mechanisms known to control volume in many cell types13, this stands as a remarkable mechanism for increasing cell size and regulating growth rate. It is, however, the duration of the final phase of volume enlargement by proportional dry mass increase at low density that varies most between rapidly and slowly elongating growth plates. Moreover, we find that this third phase is locally regulated through an Insulin-like Growth Factor-dependent mechanism. This study provides a framework for understanding how skeletal size is regulated and for exploring how cells sense, modify, and establish a volume set point.en
dc.language.isoen_USen
dc.relation.isversionofdoi:10.1038/nature11940en
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3606657/pdf/en
dash.licenseLAAen_US
dc.titleMultiple Phases of Chondrocyte Enlargement Underlie Differences in Skeletal Proportionsen
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden
dc.relation.journalNatureen
dash.depositing.authorOh, Seungeunen_US
dc.date.available2014-03-10T16:17:46Z
dc.identifier.doi10.1038/nature11940*
dash.contributor.affiliatedOh, Seungeun
dash.contributor.affiliatedKirschner, Marc
dash.contributor.affiliatedTabin, Clifford


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