Sclerostin stimulates osteocyte support of osteoclast activity by a RANKL-dependent pathway.
Sclerostin stimulates osteocyte support of osteoclast activity by a RANKL-dependent pathway.
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DOI：
10.1371/journal.pone.0025900
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Atkins GJ
中科院分区：
文献类型：
--
作者：
Wijenayaka AR;Kogawa M;Lim HP;Bonewald LF;Findlay DM;Atkins GJ
Sclerostin is a product of mature osteocytes embedded in mineralised bone and is a negative regulator of bone mass and osteoblast differentiation. While evidence suggests that sclerostin has an anti-anabolic role, the possibility also exists that sclerostin has catabolic activity. To test this we treated human primary pre-osteocyte cultures, cells we have found are exquisitely sensitive to sclerostin, or mouse osteocyte-like MLO-Y4 cells, with recombinant human sclerostin (rhSCL) and measured effects on pro-catabolic gene expression. Sclerostin dose-dependently up-regulated the expression of receptor activator of nuclear factor kappa B (RANKL) mRNA and down-regulated that of osteoprotegerin (OPG) mRNA, causing an increase in the RANKL∶OPG mRNA ratio. To examine the effects of rhSCL on resulting osteoclastic activity, MLO-Y4 cells plated onto a bone-like substrate were primed with rhSCL for 3 days and then either mouse splenocytes or human peripheral blood mononuclear cells (PBMC) were added. This resulted in cultures with elevated osteoclastic resorption (approximately 7-fold) compared to untreated co-cultures. The increased resorption was abolished by co-addition of recombinant OPG. In co-cultures of MLO-Y4 cells with PBMC, SCL also increased the number and size of the TRAP-positive multinucleated cells formed. Importantly, rhSCL had no effect on TRAP-positive cell formation from monocultures of either splenocytes or PBMC. Further, rhSCL did not induce apoptosis of MLO-Y4 cells, as determined by caspase activity assays, demonstrating that the osteoclastic response was not driven by dying osteocytes. Together, these results suggest that sclerostin may have a catabolic action through promotion of osteoclast formation and activity by osteocytes, in a RANKL-dependent manner.
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影响因子：
4.1
作者：
Atkins, Gerald J.;Anderson, Paul H.;Morris, Howard A.
通讯作者：
Morris, Howard A.
影响因子：
6.2
作者：
Kogianni, Giolanta;Mann, Val;Noble, Brendon S.
通讯作者：
Noble, Brendon S.
影响因子：
3.7
作者：
Choi HY;Dieckmann M;Herz J;Niemeier A
通讯作者：
Niemeier A
影响因子：
4
作者：
Balemans, W;Patel, N;Van Hul, W
通讯作者：
Van Hul, W
影响因子：
5.3
作者：
Kramer, Ina;Halleux, Christine;Kneissel, Michaela
通讯作者：
Kneissel, Michaela