Macrophage migration inhibitory factor inhibits osteoclastogenesis

Jacquin, Claire; Koczon-Jaremko, Boguslawa; Aguila, Héctor L.; Leng, Lin; Bucala, Richard; Kuchel, George A.; Lee, Sun-Kyeong

doi:10.1016/j.bone.2009.06.028

Cited by 44 publications

(43 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…This is consistent with our previous report that showed that an ovariectomy-induced increase in the number of osteoclasts and bone resorption in the femur of WT did not occur in MIF KO [15]. Jacquin et al recently reported that the bone volume of MIF KO was reduced due to increased osteoclastogenesis in vivo and showed that MIF inhibited osteoclastogenesis by inhibiting RANKL activity in ex vivo experiments [16]. Their report suggests that the number of osteoclasts within the fracture callus in MIF KO may be increased, which is inconsistent with our results.…”

Section: Delayed Bone Turnover and Disordered Mineralization Of Osteosupporting

confidence: 82%

Impaired fracture healing in macrophage migration inhibitory factor-deficient mice

et al. 2010

View full text Add to dashboard Cite

show abstract

Section: Delayed Bone Turnover and Disordered Mineralization Of Osteosupporting

confidence: 82%

Impaired fracture healing in macrophage migration inhibitory factor-deficient mice

et al. 2010

View full text Add to dashboard Cite

show abstract

“…The suppressive effect of MIF on the formation of MNCs was most remarkable when applied at the middle stage. The present results are consistent with a recent report demonstrating that the formation of MNCs in a culture of RAW 264.7 cells, a mouse macrophage cell line, was suppressed more effectively in the presence of RANKL when MIF was applied at the last 2 days in a 4-day culture (19). It is noteworthy that the middle stage in our experiment coincides with the time when multinuclear osteoclasts were first confirmed in the same co-culture system (27).…”

Section: Effects Of Mif On Osteoclast Formation In the Co-culturesupporting

confidence: 82%

“…The large resorption pits formed on the dentin surface mean strong phagocytic action of giant osteoclasts. Taken together with the results reported by another group (19), it can be concluded that MIF inhibits the formation of MNCs by preventing the fusion of osteoclastic cells.…”

Section: Discussionsupporting

confidence: 54%

“…Although analyses of bone marrow cells isolated from both wild-type and MIF transgenic mice have not provided evidence of the direct effects of MIF on osteoclast formation (18), it has been shown that trabecular bone volume in the femurs and vertebrae of MIF-deficient mice is decreased compared to wild-type mice, suggesting that MIF-deficiency facilitates osteoclastic bone resorption (19). Osteoblasts or stromal cells play a role in osteoclast differentiation, and the interaction of these cells with osteoclast precursors is crucial for the formation of mature osteoclasts (20).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Stage-dependent suppression of the formation of dentin-resorbing multinuclear cells with migration inhibitory factor in vitro

Kikuiri

Yoshimura

Tabata

et al. 2011

Experimental and Therapeutic Medicine

View full text Add to dashboard Cite

Abstract. The macrophage migration inhibitory factor (MIF) is a crucial mediator of immune responses and is known to play a pivotal role in cell proliferation and differentiation. In this study, we assessed whether MIF exerts regulatory effects on osteoclast formation in bone marrow cells and, if so, by what mechanism. Bone marrow cells were either co-cultured with MC3T3-E1 cells or cultured with macrophage-colony stimulating factor (M-CSF) and the soluble form of the receptor activator of the nuclear factor-κB ligand (RANKL). Under the influence of MIF, the formation of osteoclastic multinuclear cells was examined. The number of multinuclear TRAP-positive cells formed in the co-culture was significantly reduced when MIF (≥0.1 µg/ml) was exogenously applied during the third and fourth days of the 6-day cultivation period. MIF affected neither the number of mononuclear TRAP-positive cells induced with M-CSF and RANKL, nor the expression of RANKL and osteoprotegerin in MC3T3-E1 cells. TRAP-positive cells cultured on dentin slices with MIF showed lower dentin-resorbing activity than those cultured without MIF. These results suggest that MIF has no regulatory roles in the differentiation of bone marrow cells to mononuclear TRAP-positive cells, but has inhibitory effects on the formation of mature osteoclasts by preventing cell fusion, which may eventually interfere with the osteoclast-mediated dentin resorption.

show abstract

“…Interestingly, MIF was also shown to inhibit osteoclastogenesis in the in vitro and in vivo assays [58]. Thus, loss of MIF may be required during the formation of osteolytic bone metastases.…”

Section: Resultsmentioning

confidence: 99%

ABCC5 supports osteoclast formation and promotes breast cancer metastasis to bone

et al. 2012

View full text Add to dashboard Cite

IntroductionBone is the most common site of breast cancer metastasis, and complications associated with bone metastases can lead to a significantly decreased patient quality of life. Thus, it is essential to gain a better understanding of the molecular mechanisms that underlie the emergence and growth of breast cancer skeletal metastases.MethodsTo search for novel molecular mediators that influence breast cancer bone metastasis, we generated gene-expression profiles from laser-capture microdissected trephine biopsies of both breast cancer bone metastases and independent primary breast tumors that metastasized to bone. Bioinformatics analysis identified genes that are differentially expressed in breast cancer bone metastases compared with primary, bone-metastatic breast tumors.ResultsABCC5, an ATP-dependent transporter, was found to be overexpressed in breast cancer osseous metastases relative to primary breast tumors. In addition, ABCC5 was significantly upregulated in human and mouse breast cancer cell lines with high bone-metastatic potential. Stable knockdown of ABCC5 substantially reduced bone metastatic burden and osteolytic bone destruction in mice. The decrease in osteolysis was further associated with diminished osteoclast numbers in vivo. Finally, conditioned media from breast cancer cells with reduced ABCC5 expression failed to induce in vitro osteoclastogenesis to the same extent as conditioned media from breast cancer cells expressing ABCC5.ConclusionsOur data suggest that ABCC5 functions as a mediator of breast cancer skeletal metastasis. ABCC5 expression in breast cancer cells is important for efficient osteoclast-mediated bone resorption. Hence, ABCC5 may be a potential therapeutic target for breast cancer bone metastasis.

show abstract

Macrophage migration inhibitory factor inhibits osteoclastogenesis

Cited by 44 publications

References 36 publications

Impaired fracture healing in macrophage migration inhibitory factor-deficient mice

Impaired fracture healing in macrophage migration inhibitory factor-deficient mice

Stage-dependent suppression of the formation of dentin-resorbing multinuclear cells with migration inhibitory factor in vitro

ABCC5 supports osteoclast formation and promotes breast cancer metastasis to bone

Contact Info

Product

Resources

About