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J. Biol. Chem., Vol. 283, Issue 28, 19678-19690, July 11, 2008

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Lysosome Dispersion in Osteoblasts Accommodates Enhanced Collagen Production during Differentiation^*

Noushin Nabavi¹, Yulia Urukova, Marco Cardelli^¶, Jane E. Aubin^¶||, and Rene E. Harrison²

From the Departments of Cell and Systems Biology, Biological Sciences, ^¶Medical Biophysics, and ^||Molecular Genetics, Faculty of Medicine, University of Toronto Scarborough, Toronto, Ontario M1C 1A4 Canada

Lysosomes are essential organelles for intracellular degradation and are generally sequestered near the cell center to receive vesicles with contents targeted for destruction. During ascorbic acid (AA)-induced differentiation of osteogenic cells ( Beck, G. R., Jr., Zerler, B., and Moran, E. (2001) Cell Growth Differ. 12, 61-83[Abstract/Free Full Text] ), we saw a marked increase in total lysosome organelles in osteoblastic cells, in addition to an enhanced endocytic rate. Interestingly, lysosomes were dispersed toward the cell periphery in differentiating osteoblasts. We determined that lysosome dispersion in differentiated osteoblasts required intact microtubules for long range transport and was dependent on kinesin motors but did not involve cytosolic acidification. Impairment of lysosome dispersion markedly reduced AA-induced osteoblast differentiation. Lysosomes were not secreted in differentiated osteoblasts, implicating them instead in intracellular degradation. We assayed the degradative capacity and saw a significant increase in DQ-ovalbumin fluorescence in differentiated osteogenic cells compared with undifferentiated control cells. Osteogenic cells are specialized for type I collagen production, and we noted enhanced secreted and intracellular collagen in AA-differentiated osteoblasts versus control cells. Importantly, osteoblasts displayed procollagen-containing vesicles that were distributed throughout the cytoplasm, a portion of which colocalized with lysosomes. Treatment of cells with 2,2'-dipyridyl to inhibit procollagen trimerization enhanced colocalization of lysosomes with procollagen-containing organelles, implicating dispersed lysosomes in collagen processing in osteogenic cells.

Received for publication, April 1, 2008 , and in revised form, April 22, 2008.

^* This work was supported by a Natural Science and Engineering Research Council (NSERC) grant and funding from the Canadian Space Agency (to R. E. H.) and Canadian Institutes of Health Research (CIHR) Grant FRN 83704 (to J. E. A.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The on-line version of this article (available at http://www.jbc.org) contains supplemental Fig. 1 and Movies 2E, 6A, and 6B.

¹ Recipient of a 2008 General Motors Women in Sciences and Mathematics Scholarship.

² Recipient of an Ontario Early Researcher Award and a CIHR New Investigator award. To whom correspondence should be addressed: Dept. of Cell and Systems Biology, University of Toronto Scarborough, Toronto, Ontario M1C 1A4, Canada. Tel.: 416-287-7377; Fax: 416-287-7642; E-mail: harrison{at}utsc.utoronto.ca.

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