TY - JOUR
T1 - TNF-α and RANKL promote osteoclastogenesis by upregulating RANK via the NF-κB pathway
AU - Luo, Gang
AU - Li, Fangfei
AU - Li, Xiaoming
AU - Wang, Zheng Guo
AU - Zhang, Bo
N1 - Funding Information:
The present study was supported by the Ministry of Science and Technology (grant no. 011cb964701).
PY - 2018/5
Y1 - 2018/5
N2 - Although tumor necrosis factor alpha (TNF-α) is known to serve a critical role in the pathogenesis of inflammatory osteolysis, the exact mechanisms underlying the effects of TNF-α on osteoclast recruitment and differentiation remain unclear. To investigate the mechanisms by which TNF-α influences osteoclast differentiation, mouse bone marrow-derived macrophages (BMMs) were used as osteoclast precursors, and osteoclastogenesis was induced by macrophage colony-stimulating factor and receptor activator of nuclear factor (NF)-κB ligand (RANKL) with or without TNF-α for 4 days. Then, NF-κB was inhibited using the inhibitor, BAY 11-7082. The results indicated that treatment with TNF-α alone did not induce osteoclastogenesis of BMMs. However, TNF-α in combination with RANKL dramatically stimulated the differentiation of osteoclasts and positively regulated the expression of mRNA markers of osteoclasts. Finally, treatment of BMMs with BAY 11-7082 prevented the formation of mature osteoclasts by BMMs treated with TNF-α only or with RANKL, as well as the upregulation of osteoclast marker genes. Therefore, although TNF-α does not induce osteoclastogenesis alone, it does work with RANKL to induce osteoclastic differentiation, and the NF-κB pathway may serve an important role in this process.
AB - Although tumor necrosis factor alpha (TNF-α) is known to serve a critical role in the pathogenesis of inflammatory osteolysis, the exact mechanisms underlying the effects of TNF-α on osteoclast recruitment and differentiation remain unclear. To investigate the mechanisms by which TNF-α influences osteoclast differentiation, mouse bone marrow-derived macrophages (BMMs) were used as osteoclast precursors, and osteoclastogenesis was induced by macrophage colony-stimulating factor and receptor activator of nuclear factor (NF)-κB ligand (RANKL) with or without TNF-α for 4 days. Then, NF-κB was inhibited using the inhibitor, BAY 11-7082. The results indicated that treatment with TNF-α alone did not induce osteoclastogenesis of BMMs. However, TNF-α in combination with RANKL dramatically stimulated the differentiation of osteoclasts and positively regulated the expression of mRNA markers of osteoclasts. Finally, treatment of BMMs with BAY 11-7082 prevented the formation of mature osteoclasts by BMMs treated with TNF-α only or with RANKL, as well as the upregulation of osteoclast marker genes. Therefore, although TNF-α does not induce osteoclastogenesis alone, it does work with RANKL to induce osteoclastic differentiation, and the NF-κB pathway may serve an important role in this process.
KW - Nuclear factor-κB
KW - Osteoclast
KW - Receptor activator of nuclear factor-κB
KW - Tumor necrosis factor α
UR - http://www.scopus.com/inward/record.url?scp=85044623199&partnerID=8YFLogxK
U2 - 10.3892/mmr.2018.8698
DO - 10.3892/mmr.2018.8698
M3 - Journal article
C2 - 29512766
AN - SCOPUS:85044623199
SN - 1791-2997
VL - 17
SP - 6605
EP - 6611
JO - Molecular Medicine Reports
JF - Molecular Medicine Reports
IS - 5
ER -