Evidence for lysosomal exocytosis and release of aggrecan-degrading hydrolases from hypertrophic chondrocytes, in vitro and in vivo

Bastow, Edward R., Last, Karena, Golub, Sue, Stow, Jennifer L., Stanley, Amanda C. and Fosang, Amanda J. (2012) Evidence for lysosomal exocytosis and release of aggrecan-degrading hydrolases from hypertrophic chondrocytes, in vitro and in vivo. Biology Open, 1 4: 318-328. doi:10.1242/bio.2012547

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Author Bastow, Edward R.
Last, Karena
Golub, Sue
Stow, Jennifer L.
Stanley, Amanda C.
Fosang, Amanda J.
Title Evidence for lysosomal exocytosis and release of aggrecan-degrading hydrolases from hypertrophic chondrocytes, in vitro and in vivo
Formatted title
Evidence for lysosomal exocytosis and release of aggrecan-degrading hydrolases from hypertrophic chondrocytes, in vitro and in vivo
Journal name Biology Open   Check publisher's open access policy
ISSN 2046-6390
Publication date 2012-04-15
Sub-type Article (original research)
DOI 10.1242/bio.2012547
Open Access Status DOI
Volume 1
Issue 4
Start page 318
End page 328
Total pages 11
Place of publication Cambridge, United Kingdom
Publisher The Company of Biologists
Collection year 2013
Language eng
Formatted abstract
The abundant proteoglycan, aggrecan, is resorbed from growth plate cartilage during endochondral bone ossification, yet mice with genetically-ablated aggrecan-degrading activity have no defects in bone formation. To account for this apparent anomaly, we propose that lysosomal hydrolases degrade extracellular, hyaluronan-bound aggrecan aggregates in growth plate cartilage, and that lysosomal hydrolases are released from hypertrophic chondrocytes into growth plate cartilage via Ca2+-dependent lysosomal exocytosis. In this study we confirm that hypertrophic chondrocytes release hydrolases via lysosomal exocytosis in vitro and we show in vivo evidence for lysosomal exocytosis in hypertrophic chondrocytes during skeletal development. We show that lysosome-associated membrane protein 1 (LAMP1) is detected at the cell surface following in vitro treatment of epiphyseal chondrocytes with the calcium ionophore, ionomycin. Furthermore, we show that in addition to the lysosomal exocytosis markers, cathepsin D and β-hexosaminidase, ionomycin induces release of aggrecan- and hyaluronan-degrading activity from cultured epiphyseal chondrocytes. We identify VAMP-8 and VAMP7 as v-SNARE proteins with potential roles in lysosomal exocytosis in hypertrophic chondrocytes, based on their colocalisation with LAMP1 at the cell surface in secondary ossification centers in mouse tibiae. We propose that resorbing growth plate cartilage involves release of destructive hydrolases from hypertrophic chondrocytes, via lysosomal exocytosis.
Keyword Aggrecan
Endochondral bone formation
Growth plate
Hyaluronidase
Hypertrophic chondrocyte
Lysosomal exocytosis
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2013 Collection
Institute for Molecular Bioscience - Publications
 
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Citation counts: TR Web of Science Citation Count  Cited 4 times in Thomson Reuters Web of Science Article | Citations
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Created: Fri, 14 Dec 2012, 11:06:27 EST by Susan Allen on behalf of Institute for Molecular Bioscience