Impaired fracture healing in macrophage migration inhibitory factor-deficient mice

Kobayashi, Takumi; Onodera, Shin; Kondo, Eiji; Tohyama, Harukazu; Fujiki, Hiroyuki; Yokoyama, Akihisa; Yasuda, Kazunori

doi:10.1007/s00198-010-1385-0

Cited by 19 publications

(23 citation statements)

References 35 publications

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“…Our findings are in line with those of all other papers on this area[21-23,46], other than Jacquin et al and Mun et al . There are key differences between the current study and that Jacquin et al .…”

Section: Discussionsupporting

confidence: 94%

“…MIF -/- mice exhibit protection from bone loss induced by ovariectomy[21] and periodontal disease[22]. MIF -/- mice show lower osteoclast numbers at fracture callus[23], and elevated bone resorption is seen in MIF transgenic mice[24]. However, Jacquin et al [25] have reported the converse, that MIF reduced osteoclastogenesis in vitro , and that MIF -/- mice have significantly reduced trabecular bone mass.…”

Section: Introductionmentioning

confidence: 99%

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Macrophage migration inhibitory factor is essential for osteoclastogenic mechanisms in vitro and in vivo mouse model of arthritis

Santos

Ngo

et al. 2015

Cytokine

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Macrophage migration inhibitory factor (MIF) enhances activation of leukocytes, endothelial cells and fibroblast-like synoviocytes (FLS), thereby contributing to the pathogenesis of rheumatoid arthritis (RA). A MIF promoter polymorphism in RA patients resulted in higher serum MIF concentration and worsens bone erosion; controversially current literature reported an inhibitory role of MIF in osteoclast formation. The controversial suggested that the precise role of MIF and its putative receptor CD74 in osteoclastogenesis and RA bone erosion, mediated by locally formed osteoclasts in response to receptor activator of NF-κB ligand (RANKL), is unclear. We reported that in an in vivo K/BxN serum transfer arthritis, reduced clinical and histological arthritis in MIF-/- and CD74-/- mice were accompanied by a virtual absence of osteoclasts at the synovium-bone interface and reduced osteoclast-related gene expression. Furthermore, in vitro osteoclast formation and osteoclast-related gene expression were significantly reduced in MIF-/- cells via decreasing RANKL-induced phosphorylation of NF-κB-p65 and ERK1/2. This was supported by a similar reduction of osteoclastogenesis observed in CD74-/- cells. Furthermore, a MIF blockade reduced RANKL-induced osteoclastogenesis via deregulating RANKL-mediated NF-κB and NFATc1 transcription factor activation. These data indicate that MIF and CD74 facilitate RANKL-induced osteoclastogenesis, and suggest that MIF contributes directly to bone erosion, as well as inflammation, in RA.

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Section: Discussionsupporting

confidence: 94%

Section: Introductionmentioning

confidence: 99%

Macrophage migration inhibitory factor is essential for osteoclastogenic mechanisms in vitro and in vivo mouse model of arthritis

Santos

Ngo

et al. 2015

Cytokine

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“…Radiographs of the right and left femurs were taken at 2, 4, and 6 weeks after fracture by using an X-ray unit (SkyScan 1074, Toyo Co., Tokyo, Japan). The callus area at the fracture site was measured at 2 weeks after fracture because this area is known to peak at this time point in mice [1], [2]. The degree of callus formation was calculated as the ratio of the callus area to the femoral bone diameter at the fracture gap [16].…”

Section: Methodsmentioning

confidence: 99%

“…Bone regeneration after fracture occurs in the following consecutive phases: callus formation around the fracture site, osteoid formation, mineralization within the callus, and callus resorption [1], [2]. Although the molecular mechanisms underlying these phases are not fully understood, impairment of callus formation is known to delay fracture healing [2]. Mineralization of the osteoid, an essential component of the fracture healing process is regulated by alkaline phosphatase (ALP) [3].…”

Section: Introductionmentioning

confidence: 99%

Hyperbaric Hyperoxia Accelerates Fracture Healing in Mice

et al. 2013

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Increased oxygen tension influences bone metabolism. This study comprised two main experiments: one aimed to determine the bone mineral apposition and bone formation rates in vivo under hyperbaric hyperoxia (HBO), and the other aimed to evaluate the effects of exposure to HBO on fracture healing. In experiment 1, male mice were exposed to HBO [90 min/day at 90% O2 at 2 atmospheres absolute (ATA) for 5 days]. In experiment 2, an open femur fracture model was created in mice, followed by exposure to HBO 5 times/week (90 min/day at 90% O2 at 2 ATA) for 6 weeks after surgery. In experiment 1, HBO treatment significantly increased the mineral apposition and bone formation rates in the lumbar vertebra and femur and type 1 collagen alpha 1 and alkaline phosphatase mRNA expression in the lumbar vertebra. In experiment 2, at 2 weeks after fracture, the fracture callus was significantly larger in the HBO group than in the non-HBO group. Furthermore, at 4 and 6 weeks after fracture, radiographic findings showed accelerated fracture healing in the HBO group. At 6 weeks after fracture, femur stiffness and maximum load were significantly higher in the HBO group than in the non-HBO group. Urinary 8-hydroxy-2′-deoxyguanosine and plasma calcium concentrations were not significantly different between groups. These results suggest that exposure to HBO enhances bone anabolism and accelerates fracture healing without causing oxidative DNA damage or disruption of plasma calcium homeostasis.

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“…M2b have also been found in circulation and peripheral tissues following severe burns, supporting a systemic activity for this subset [40,41].…”

Section: Disease Associationsmentioning

confidence: 73%

Macrophage and Multinucleated Giant Cell Classification

Trout

Jessop

Migliaccio

2016

Current Topics in Environmental Health and Preventive Medicine

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The purpose of this chapter is to provide an overview of macrophage subtype and multinucleated giant cell classification with a specific discussion of their role(s) in response to particulates and other foreign bodies. Topics covered for the different subtypes include the following: environmental factors involved in their generation, functional characterization, disease associations, and interactions with particulates. This chapter is separated into three major parts. The first portion describes the normal structure and functions of the macrophage. Second, the currently published macrophage subsets are outlined. The classifications included in the discussion are based on function ("M" polarization) rather than anatomical position (tissue-specific macrophages -Kupffer cells, alveolar macrophages, etc.). As shown in Fig. 1.1, the ontogeny of the various types of macrophages being discussed in this chapter depends on the pathway of activation. The third major section focuses on multinucleated giant cells, which are formed by fusion of individual macrophages. The ontogeny of each subset will be discussed and the current literature regarding particulate/foreign-body interaction will be reviewed.

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Impaired fracture healing in macrophage migration inhibitory factor-deficient mice

Abstract: The results of the present study suggest that delayed fracture healing in MIF KO was mainly attributable to a delay in osteoid mineralization.

Cited by 19 publications

References 35 publications

Macrophage migration inhibitory factor is essential for osteoclastogenic mechanisms in vitro and in vivo mouse model of arthritis

Macrophage migration inhibitory factor is essential for osteoclastogenic mechanisms in vitro and in vivo mouse model of arthritis

Hyperbaric Hyperoxia Accelerates Fracture Healing in Mice

Macrophage and Multinucleated Giant Cell Classification

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