Chemokine and chemokine receptor expression during colony stimulating factor-1-induced osteoclast differentiation in the toothless osteopetrotic rat: a key role for CCL9 (MIP-1gamma) in osteoclastogenesis in vivo and in vitro
Authors
Yang, MeilhengMailhot, Genevieve
MacKay, Carole A.
Mason-Savas, April
Aubin, Justin
Odgren, Paul R.
UMass Chan Affiliations
Dept of Cell BiologyDocument Type
Journal ArticlePublication Date
2005-11-24Keywords
AnimalsCathepsins
Cell Differentiation
Cell Proliferation
Chemokines, CC
Gene Expression Profiling
Glycoproteins
Macrophage Colony-Stimulating Factor
Macrophage Inflammatory Proteins
Osteoclasts
Osteopetrosis
Osteoprotegerin
RNA
Rats
Rats, Inbred Strains
Receptor, Macrophage Colony-Stimulating Factor
Receptors, CCR1
Receptors, Chemokine
Receptors, Cytoplasmic and Nuclear
Receptors, Tumor Necrosis Factor
Cell and Developmental Biology
Cell Biology
Metadata
Show full item recordAbstract
Osteoclasts differentiate from hematopoietic precursors under systemic and local controls. Chemokines and receptors direct leukocyte traffic throughout the body and may help regulate site-specific bone resorption. We investigated bone gene expression in vivo during rapid osteoclast differentiation induced by colony-stimulating factor 1 (CSF-1) in Csf1-null toothless (tl/tl) rats. Long-bone RNA from CSF-1-treated tl/tl rats was analyzed by high-density microarray over a time course. TRAP (tartrate-resistant acid phosphatase)-positive osteoclasts appeared on day 2, peaked on day 4, and decreased slightly on day 6, as marrow space was expanding. TRAP and cathepsin K mRNA paralleled the cell counts. We examined all chemokine and receptor mRNAs on the arrays. CCL9 was strongly induced and peaked on day 2, as did its receptor, CCR1, and regulatory receptors c-Fms (CSF-1 receptor) and RANK (receptor activator of nuclear factor kappaB). Other chemokines and receptors showed little or no significant changes. In situ hybridization and immunohistochemistry revealed CCL9 in small, immature osteoclasts on day 2 and in mature cells at later times. Anti-CCL9 antibody inhibited osteoclast differentiation in culture and significantly suppressed the osteoclast response in CSF-1-treated tl/tl rats. While various chemokines have been implicated in osteoclastogenesis in vitro, this first systematic analysis of chemokines and receptors during osteoclast differentiation in vivo highlights the key role of CCL9 in this process.Source
Blood. 2006 Mar 15;107(6):2262-70. Epub 2005 Nov 22. Link to article on publisher's siteDOI
10.1182/blood-2005-08-3365Permanent Link to this Item
http://hdl.handle.net/20.500.14038/39940PubMed ID
16304045Related Resources
Link to article in PubMedae974a485f413a2113503eed53cd6c53
10.1182/blood-2005-08-3365
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