Tumor necrosis factor-alpha alters the modulatory effects of mesenchymal stem cells on osteoclast formation and function.
Mesenchymal stem cells (MSCs) are characterized by their hematopoiesis-supporting and immunosuppressive capacity, while osteoclasts are main cell components in the endosteal hematopoietic stem cell niche and pivotal players in osteoimmunology. To clarify the association of these 2 kinds of cells, mouse CD11b(+) monocytes were cultured onto MSC layers in the presence or absence of macrophage colony-stimulating factor (M-CSF) and receptor activator of NF-kappaB ligand (RANKL). The results showed that MSCs independently supported osteoclast development and this effect was enhanced by M-CSF and RANKL. Interestingly, tumor necrosis factor-alpha (TNF-alpha)-stimulated MSCs turned to inhibit osteoclast formation and protect tusk slices from osteoclastic resorption. Real-time PCR and ELISA assays demonstrated that osteoprotegerin expression at both mRNA and protein levels in TNF-alpha-stimulated MSCs was up-regulated, at least partially by activating the mitogen-activated protein kinase pathway. Furthermore, TNF-alpha-stimulated MSCs maintained their immunophenotypic, multipotential differentiation and immunosuppressive characteristics. Moreover, MSCs treated with synovial fluid from rheumatoid arthritis patients modulated osteoclast generation in close relation with the TNF-alpha levels. This study suggests that MSCs exhibit dual modulatory function on osteoclasts and the result might shed light on understanding the involvement of MSCs in the inflammatory diseases.
Department of Cell Biology, Institute of Basic Medical Sciences, Beijing 100850, People's Republic of China.
Heng
H
Zhu
Xiao-Xia
XX
Jiang
Zi-Kuan
ZK
Guo
Hong
H
Li
Yong-Feng
YF
Su
Hui-Yu
HY
Yao
Xiao-Yan
XY
Wang
Xiu-Sen
XS
Li
Ying
Y
Wu
Yuan-Lin
YL
Liu
Yi
Y
Zhang
Ning
N
Mao
D000818:Animals; D001172:Arthritis, Rheumatoid / Q000473:pathology; D039481:CD11b Antigen / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D006801:Humans; D007108:Immune Tolerance / Q000187:drug effects; D016130:Immunophenotyping; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D039902:Multipotent Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D010010:Osteoclasts / Q000166:cytology* / Q000187:drug effects* / Q000201:enzymology; D053244:Osteoprotegerin / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012995:Solubility / Q000187:drug effects; D013582:Synovial Fluid / Q000166:cytology / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects
D039481:CD11b Antigen; D053244:Osteoprotegerin; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D020928:Mitogen-Activated Protein Kinases