RT Journal Article
SR Electronic
T1 Roles of chemokine receptor CX3CR1 in maintaining murine bone homeostasis through the regulation of both osteoblasts and osteoclasts
JF Journal of Cell Science
JO J. Cell Sci.
FD The Company of Biologists Ltd
SP 1032
OP 1045
DO 10.1242/jcs.113910
VO 126
IS 4
A1 Hoshino, Akiyoshi
A1 Ueha, Satoshi
A1 Hanada, Sanshiro
A1 Imai, Toshio
A1 Ito, Masako
A1 Yamamoto, Kenji
A1 Matsushima, Kouji
A1 Yamaguchi, Akira
A1 Iimura, Tadahiro
YR 2013
UL http://jcs.biologists.org/content/126/4/1032.abstract
AB Chemokines have recently been reported to be involved in pathological bone destruction. However, the physiological roles of chemokines in bone metabolism in vivo have not been well documented. We analyzed the bone phenotypes in Cx3cr1-deficient mice. The mice exhibited slight but significant increases in trabecular and cortical thickness, reduced numbers of osteoclasts and increased rates of osteoid formation. Although the morphometric parameters showed marginal differences, the Cx3cr1-deficient bones showed an elevated expression of Osterix/SP7, which encodes an essential transcriptional factor for osteoblasts, whereas the gene Osteocalcin/Bglap, which encodes a late marker, was downregulated. The levels of transcripts for various osteoclastic markers, such as receptor activator of NF-κB (RANK)/TNFRSF11A, receptor activator of NF-κB ligand (RANKL)/TNFSF11, tartrate-resistant acid phosphatase 5b (TRAP5B)/ACP5B, Cathepsin K(CTSK), MMP3 and MMP13, were significantly decreased in the Cx3cr1-deficient bones. Cultured Cx3cr1-deficient osteoblastic cells showed inverse temporal patterns of osteoblastic marker expression and reduced calcium deposition. Furthermore, in vitro studies and immunofluorescence staining against CX3CR1 and CX3CL1 suggested a role for the CX3CR1–CX3CL1 axis in an early stage of osteoblast differentiation, possibly through their trans and cis interactions. Cultured Cx3cr1-deficient pre-osteoclasts showed impaired differentiation, mainly due to a deficiency of the CD115+CD11blo osteoclastogenic population of myeloid-lineage precursors. The treatment of bone-marrow-derived osteoclastic cultures with recombinant CX3CL1 at different time points suggested that the CX3CR1–CX3CL1 axis favors the maintenance of osteoclastic precursors, but not differentiated osteoclasts. These observations uncovered novel roles of the CX3CR1–CX3CL1 axis in the differentiation of both osteoblasts and osteoclasts.