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Publication : Roles of matricellular CCN2 deposited by osteocytes in osteoclastogenesis and osteoblast differentiation.

First Author  Nishida T Year  2019
Journal  Sci Rep Volume  9
Issue  1 Pages  10913
PubMed ID  31358778 Mgi Jnum  J:285606
Mgi Id  MGI:6387614 Doi  10.1038/s41598-019-47285-3
Citation  Nishida T, et al. (2019) Roles of matricellular CCN2 deposited by osteocytes in osteoclastogenesis and osteoblast differentiation. Sci Rep 9(1):10913
abstractText  In this study, we investigated the effect of CCN2 (cellular communication network factor 2), previously termed connective tissue growth factor, deposited in bone matrix on osteoclastogenesis and osteoblast differentiation. To mimic the bone matrix environment, osteocytic MLO-Y4 cells had been embedded in collagen-gel with recombinant CCN2 (rCCN2), and mouse macrophage-like RAW264.7 cells were inoculated on the gel and treated with receptor activator of NF-kappaB ligand (RANKL). NFATc1 and cathepsin K (CTSK) productions were more increased in the combination of RAW264.7 and MLO-Y4 cells treated with rCCN2 than the combination without rCCN2. Next, we isolated an osteocyte-enriched population of cells and osteoclast progenitor cells from wild type and tamoxifen-inducible Ccn2-deficient (KO) mice and performed similar analysis. NFATc1 and CTSK productions were decreased in the KO osteocyte-enriched population at 6 months after the tamoxifen injection, regardless of the origin of the osteoclast progenitor cells. Interestingly, CTSK production was rather increased in KO osteocytes at 1 year after the injection. Finally, the combination of osteoblastic MC3T3-E1 and MLO-Y4 cells in rCCN2-containing bone matrix revealed the up-regulation of osteoblastic marker genes. These findings suggest that CCN2 supplied by osteocytes regulates both osteoclastogenesis and osteoblast differentiation.
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