Estrogen Deficiency–Mediated M2 Macrophage Osteoclastogenesis Contributes to M1/M2 Ratio Alteration in Ovariectomized Osteoporotic Mice

Dou, Ce; Ding, Ning; Zhao, Chunrong; Hou, Tianyong; Kang, Fei; Cao, Zhen; Liu, Chuan; Bai, Yun; Dai, Qijie; Ma, Qinyu; Luo, Fei; Xu, Jiake; Dong, Shiwu

doi:10.1002/jbmr.3364

Cited by 122 publications

(83 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We assume that the immunomodulatory and anti-inflammatory activities of physalin D were likely to be realized by its regulation of macrophage polarization toward the M2 phenotype shift. One of our recent studies interestingly showed that M1/M2 ratio alteration also contribute to the pathogenesis of estrogen-deficiency-induced osteoporosis which further reinforced the idea that M1/M2 polarization is a target of great potential in treating related chronic diseases (Dou et al, 2018).…”

mentioning

confidence: 61%

Physalin D regulates macrophage M1/M2 polarization via the STAT1/6 pathway

Ding

Wang

Dou

et al. 2018

Journal Cellular Physiology

Self Cite

View full text Add to dashboard Cite

The in vitro and in vivo effects of physalin D on macrophage M1/M2 polarization were investigated. In silico analysis was first performed for biological function prediction of different physalins. The results suggest physalins have similar predicted biological functions due to their similarities in chemical structures. The cytotoxicity of physalins was then analyzed based on cell apoptosis rate and cell viability evaluation. Physalin D was chosen for further study due to its minimal cytotoxicity. Bone marrow macrophages were isolated and induced with lipopolysaccharide/interferon (IFN)‐γ for M1 polarization and interleukin (IL)‐4/IL‐13 for M2 polarization. The results showed that physalin D can repolarize M1 phenotype cells toward M2 phenotype. In addition, physalin D is protective in M2 macrophages to maintain the M2 phenotype in the presence of IFN‐γ. On the molecular level, we found that physalin D suppressed the signal transducers and activators of transcription (STAT)1 activation and blocked STAT1 nuclear translocation. Conversely, physalin D can also activate STAT6 and enhance STAT6 nuclear translocation for M2 polarization. Taken together, these results suggested that physalin D regulates macrophage M1/M2 polarization via the STAT1/6 pathway.

show abstract

mentioning

confidence: 61%

Physalin D regulates macrophage M1/M2 polarization via the STAT1/6 pathway

Ding

Wang

Dou

et al. 2018

Journal Cellular Physiology

Self Cite

View full text Add to dashboard Cite

show abstract

“…Studies showed that M1 macrophages could down‐regulate osteoclastogenesis (47), and conversely, osteoclast‐related fusion protein may decrease M1 macrophage polarization (48). Moreover, estrogen‐deficient M2 macrophages could lead to the increased osteoclast differentiation (49). These studies exposed the potential role of M1 macrophages in inhibiting osteoclast function.…”

Section: Discussionmentioning

confidence: 99%

Zoledronic acid promotes TLR‐4‐mediated M1 macrophage polarization in bisphosphonate‐related osteonecrosis of the jaw

Zhu

et al. 2019

FASEB j.

View full text Add to dashboard Cite

Bisphosphonate‐related osteonecrosis of the jaw (BRONJ) is a detrimental side effect of the long‐term administration of bisphosphonates. Although macrophages were reported to be an important mediator of BRONJ, the detailed potential mechanism of BRONJ remains unclear. Here, we reported an elevated TLR‐4 expression in macrophages under action of zoledronic acid (ZA), resulting in enhanced M1 macrophage polarization and decreased M2 macrophage polarization both in vitro and in vivo. After inhibiting the TLR‐4 signaling pathway, the activation of the TLR‐4/NF‐κB signaling pathway and the induction of NF‐κB nuclear translocation and production of proinflammatory cytokines by ZA were suppressed in macrophages, thereby inhibiting M1 macrophage polarization. By utilizing the TLR‐4−/− mice, development of BRONJ was markedly ameliorated, and M1 macrophages were significantly attenuated in the extraction socket tissues in the TLR‐4−/− mice. Importantly, the systemic administration of the TLR‐4 inhibitor TAK‐242 improved the wound healing of the extraction socket and decreased the incidence rate of BRONJ. Taken together, our findings suggest that TLR‐4‐mediated macrophage polarization participates in the pathogenesis of BRONJ in mice, and TLR‐4 may be a potential target for the prevention and therapeutic treatment of BRONJ.—Zhu, W., Xu, R., Du, J., Fu, Y., Li, S., Zhang, P., Liu, L., Jiang, H. Zoledronic acid promotes TLR‐4‐mediated M1 macrophage polarization in bisphosphonate‐related osteonecrosis of the jaw. FASEB J. 33, 5208–5219 (2019). http://www.fasebj.org

show abstract

“…The polarisation of pro-inflammatory macrophages M1 to anti-inflammatory macrophages M2 is indicative of endochondral ossification in the long bone fracture model (Cordova et al, 2017;Loi et al, 2016;Schlundt et al, 2018). In OVX mice, M1 polarisation is enhanced while M2 polarisation is impaired, leading to increased M1/M2 ratio in the bone marrow (Dou et al, 2018). The present study results revealed that the vibration treatment brought the number of M2 macrophages to normal levels, as shown by similar CD206 level to SHAM, and induced higher CD206 expression as compared to OVX rats (Fig.…”

Section: Discussionmentioning

confidence: 99%

Vibration treatment modulates macrophage polarisation and enhances early inflammatory response in oestrogen-deficient osteoporotic-fracture healing

Chow

Chim²,

Wang³

et al. 2019

eCM

View full text Add to dashboard Cite

Fracture healing is a well-orchestrated and coordinated process and begins with the inflammatory stage involving the infiltration of immune cells and the release of cytokines, including tumour necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and interleukin-10 (IL-10). Low-magnitude high-frequency vibration (LMHFV) stimulation is effective in promoting fracture healing. The study hypothesis was that the innate immune response was impaired in osteoporotic fracture and LMHFV could positively modulate it. 9-month-old ovariectomy (OVX)-induced osteoporotic rats were randomised into sham (SHAM), OVX control (OVX), OVX-vibration (OVX-VT) or OVX vibration plus administration of COX-2 specific non-steroid anti-inflammatory drugs (OVX-VT-NSAID). LMHFV (35 Hz, 0.3 ×g) was given 20 min/d and 5 d/week to the treatment groups. Healing and innate immune response were evaluated by weekly radiographs, endpoint micro-computed tomography (µCT), enzyme-linked immunosorbent assay (ELISA) and histomorphometry at weeks 1, 2, 4 and 8 post-treatment.Results showed that OVX slightly elevated systemic inflammation but impaired the innate immune response locally at the fracture site, with significantly lower expressions of TNF-α and IL-6 but higher IL-10 expression during the early stage of healing. LMHFV was effective in accelerating the delayed fracture healing in OVX bones by partly restoring the impaired innate immune response at the fracture site, accompanied by promoted progression of macrophage polarisation from M1 (pro-inflammatory) to M2 (anti-inflammatory) phenotype. In conclusion, vibration treatment could positively modulate the impaired innate immune response and promote macrophage polarisation in osteoporotic-fracture healing.

show abstract

Estrogen Deficiency–Mediated M2 Macrophage Osteoclastogenesis Contributes to M1/M2 Ratio Alteration in Ovariectomized Osteoporotic Mice

Cited by 122 publications

References 50 publications

Physalin D regulates macrophage M1/M2 polarization via the STAT1/6 pathway

Physalin D regulates macrophage M1/M2 polarization via the STAT1/6 pathway

Zoledronic acid promotes TLR‐4‐mediated M1 macrophage polarization in bisphosphonate‐related osteonecrosis of the jaw

Vibration treatment modulates macrophage polarisation and enhances early inflammatory response in oestrogen-deficient osteoporotic-fracture healing

Contact Info

Product

Resources

About