| Blood-derived human osteoclast resorption activity is impaired by Hyaluronan-CD44 engagement via a p38-dependent mechanism. | |
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MedLine Citation:
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PMID: 20799279 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The control of bone resorption is crucial in osteolytic diseases. Once attached to bone, osteoclasts (OCs) initiate the resorption process through the activation of a complex cascade of morphological and biochemical changes. Hyaluronan (HA), an extracellular glycosaminoglycan long non-branching polysaccharide, is expressed in bone matrices. Here we demonstrate that HA counter-balances the erosion activity of human mature OCs by significantly reducing their degradative potential. HA treatment of fully differentiated OCs derived from human peripheral blood monocytes inhibited migration on collagen as well as bone resorption. HA-mediated effects were primarily due to TRAcP, MMP-9, and cathepsin K down-regulation and to the increased levels of TIMP-1, a natural MMP-9 inhibitor. Binding of HA to mature OCs was entirely mediated by CD44: function-blocking anti-CD44 antibodies fully abrogated HA effects, and the engagement of HA receptor caused a rapid de-phosphorylation of Ser325 in the CD44 cytoplasmic tail. The inhibitory action by HA was associated with a transient up-phosphorylation of Pyk2, a novel persistent phosphorylation of p38 and the down-regulation of NFATc1 transcription factor. Our results provide a direct evidence for the involvement of CD44 in the HA-dependent regulation of OC activity and suggest a signaling pathway that could be unique in OC function inhibition. |
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Authors:
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Eliana Pivetta; Martina Scapolan; Bruna Wassermann; Agostino Steffan; Alfonso Colombatti; Paola Spessotto |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Journal of cellular physiology Volume: 226 ISSN: 1097-4652 ISO Abbreviation: J. Cell. Physiol. Publication Date: 2011 Mar |
Date Detail:
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Created Date: 2010-12-30 Completed Date: 2011-01-27 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0050222 Medline TA: J Cell Physiol Country: United States |
Other Details:
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Languages: eng Pagination: 769-79 Citation Subset: IM |
Copyright Information:
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Copyright © 2010 Wiley-Liss, Inc. |
Affiliation:
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Experimental Oncology 2, CRO, IRCCS, National Cancer Institute, Aviano, PN, Italy. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Acid Phosphatase
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metabolism Antigens, CD44 / metabolism* Bone Resorption / blood*, enzymology* Cell Differentiation / drug effects Cell Movement / drug effects Cell Shape / drug effects Cell Survival / drug effects Down-Regulation / drug effects Humans Hyaluronic Acid / pharmacology* Isoenzymes / metabolism Models, Biological NFATC Transcription Factors / metabolism Osteoclasts / drug effects, enzymology*, pathology* Protein Binding / drug effects p38 Mitogen-Activated Protein Kinases / metabolism* |
| Chemical | |
Reg. No./Substance:
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0/Antigens, CD44; 0/Isoenzymes; 0/NFATC Transcription Factors; 9004-61-9/Hyaluronic Acid; EC 2.7.11.24/p38 Mitogen-Activated Protein Kinases; EC 3.1.3.-/tartrate-resistant acid phosphatase; EC 3.1.3.2/Acid Phosphatase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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