M-CSF Potently Augments RANKL-Induced Resorption Activation in Mature Human Osteoclasts

被引:73
作者
Hodge, Jason M. [1 ,2 ]
Collier, Fiona M. [2 ]
Pavlos, Nathan J. [3 ]
Kirkland, Mark A. [1 ,2 ]
Nicholson, Geoffrey C. [4 ]
机构
[1] Univ Melbourne, Dept Clin & Biomed Sci, Geelong, Vic, Australia
[2] Barwon Hlth, Barwon Biomed Res, Geelong, Vic, Australia
[3] Univ Western Australia, Sch Surg, Ctr Orthopaed Res, Nedlands, WA 6009, Australia
[4] Univ Queensland, Sch Med, Rural Clin Sch, Toowoomba, Qld, Australia
关键词
COLONY-STIMULATING FACTOR; BLOOD MONONUCLEAR-CELLS; FACTOR-KAPPA-B; BONE-RESORPTION; RECEPTOR ACTIVATOR; C-SRC; DIFFERENTIATION; OSTEOPETROSIS; FACTOR-1; EXPRESSION;
D O I
10.1371/journal.pone.0021462
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];
摘要
Macrophage-CSF (M-CSF) is critical for osteoclast (OC) differentiation and is reported to enhance mature OC survival and motility. However, its role in the regulation of bone resorption, the main function of OCs, has not been well characterised. To address this we analysed short-term cultures of fully differentiated OCs derived from human colony forming unit-granulocyte macrophages (CFU-GM). When cultured on dentine, OC survival was enhanced by M-CSF but more effectively by receptor activator of NFkB ligand (RANKL). Resorption was entirely dependent on the presence of RANKL. Co-treatment with M-CSF augmented RANKL-induced resorption in a concentration-dependent manner with a (200-300%) stimulation at 25 ng/mL, an effect observed within 4-6 h. M-CSF co-treatment also increased number of resorption pits and F-actin sealing zones, but not the number of OCs or pit size, indicating stimulation of the proportion of OCs activated. M-CSF facilitated RANKL-induced activation of c-fos and extracellular signal-regulated kinase (ERK) 1/2 phosphorylation, but not NFkB nor nuclear factor of activated T-cells, cytoplasmic-1 (NFATc1). The mitogen-activated protein kinase kinase (MEK) 1 inhibitor PD98059 partially blocked augmentation of resorption by M-CSF. Our results reveal a previously unidentified role of M-CSF as a potent stimulator of mature OC resorbing activity, possibly mediated via ERK upstream of c-fos.
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页数:8
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