Changes in macrophage and inflammatory cytokine expressions during fracture healing in an ovariectomized mice model

Chen, Lin; Cheng, Shiqiang; Sun, Kanghui; Wang, Jing; Liu, Xinhua; Zhao, Yongjian; Yang, Junjie; Zhao, Dongfeng; Xue, Cong; Tao, Yuren; Zhao, Shitian; Zhang, Hao; Lü, Sheng; Shi, Qi; Wang, Yongjun; Shu, Bing

doi:10.1186/s12891-021-04360-z

Cited by 12 publications

(11 citation statements)

References 49 publications

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“…Similar findings were reported in a study by Chen et al (62), in a mouse model of postmenopausal osteoporosis, a condition in which delayed fracture healing is also frequently observed. The authors found that both endochondral ossification and callus remodeling were impaired in ovariectomized mice (OVX), which possessed a decreased expression of TNF-α and IL-6 and a lower frequency of M1 and M2 macrophages in the fracture hematoma, respectively, on days 1 and 14 after the fracture (62).…”

Section: Relationship Of Macrophages and Fracture Impairment In The C...supporting

confidence: 91%

The role of macrophages in fracture healing: a narrative review of the recent updates and therapeutic perspectives

Frade¹,

Gemini-Piperni²,

Bonfim³

2023

Stem Cell Investig

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Objective: This review addresses the latest advances in research on the role of macrophages in fracture healing, exploring their relationship with failures in bone consolidation and the perspectives for the development of advanced and innovative therapies to promote bone regeneration. Background:The bone can fully restore its form and function after a fracture. However, the regenerative process of fracture healing is complex and is influenced by several factors, including macrophage activity.These cells have been found in the fracture site at all stages of bone regeneration, and their general depletion or the knockdown of receptors that mediate their differentiation, polarization, and/or function result in impaired fracture healing. Methods:The literature search was carried out in the PubMed database, using combinations of the keywords "macrophage", "fracture healing, "bone regeneration", and "bone repair". Articles published within the last years (2017-2022) reporting evidence from in vivo long bone fracture healing experiments were included.Conclusions: Studies published in the last five years on the role of macrophages in fracture healing strengthened the idea that what appears to be essential when it comes to a successful consolidation is the right balance between the M1/M2 populations, which have different but complementary roles in the process. These findings opened promising new avenues for the development of several macrophage-targeted therapies, including the administration of molecules and/or biomaterials intended to regulate macrophage differentiation and polarization, the local transplantation of macrophage precursors, and the use of exosomes to deliver signaling molecules that influence macrophage activities. However, more research is still warranted to better understand the diversity of macrophage phenotypes and their specific roles in each step of fracture healing and to decipher the key molecular mechanisms involved in the in vivo crosstalk between macrophages and other microenvironmental cell types, such as endothelial and skeletal stem/progenitor cells.

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Section: Relationship Of Macrophages and Fracture Impairment In The C...supporting

confidence: 91%

The role of macrophages in fracture healing: a narrative review of the recent updates and therapeutic perspectives

Frade¹,

Gemini-Piperni²,

Bonfim³

2023

Stem Cell Investig

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“…Activation patterns of the FOSL2 regulon might indicate that skeleton-endocrine functions of FOSL2 are performed predominantly by preosteoblast-S1. Previous studies showed that interactions of FOSL2 and proinflammatory cytokines, including IL-6, contributed to various inflammatory reactions [ 41 – 43 ]. In addition, FOSL2 regulon’s target gene, IL-6, was included in the core gene modules of immunity-related PPI networks.…”

Section: Discussionmentioning

confidence: 99%

Regulon active landscape reveals cell development and functional state changes of human primary osteoblasts in vivo

et al. 2023

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Background While transcription factor (TF) regulation is known to play an important role in osteoblast development, differentiation, and bone metabolism, the molecular features of TFs in human osteoblasts at the single-cell resolution level have not yet been characterized. Here, we identified modules (regulons) of co-regulated genes by applying single-cell regulatory network inference and clustering to the single-cell RNA sequencing profiles of human osteoblasts. We also performed cell-specific network (CSN) analysis, reconstructed regulon activity-based osteoblast development trajectories, and validated the functions of important regulons both in vivo and in vitro. Results We identified four cell clusters: preosteoblast-S1, preosteoblast-S2, intermediate osteoblasts, and mature osteoblasts. CSN analysis results and regulon activity-based osteoblast development trajectories revealed cell development and functional state changes of osteoblasts. CREM and FOSL2 regulons were mainly active in preosteoblast-S1, FOXC2 regulons were mainly active in intermediate osteoblast, and RUNX2 and CREB3L1 regulons were most active in mature osteoblasts. Conclusions This is the first study to describe the unique features of human osteoblasts in vivo based on cellular regulon active landscapes. Functional state changes of CREM, FOSL2, FOXC2, RUNX2, and CREB3L1 regulons regarding immunity, cell proliferation, and differentiation identified the important cell stages or subtypes that may be predominantly affected by bone metabolism disorders. These findings may lead to a deeper understanding of the mechanisms underlying bone metabolism and associated diseases.

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“… 33 In mice, the level of IL-6 reached the peak at 24h after fracture. 34 IL-6 gene is located on chromosome 7q21.3 and contains 5 exons and 4 introns. At present, its common promoter regions SNPs included rs1800796, rs1800795, rs1800797, and rs10499563.…”

Section: Discussionmentioning

confidence: 99%

Association of IL-6 and TGF-β Gene Polymorphisms with the Risk of Thoracolumbar Osteoporotic Vertebral Compression Fractures

Xiong

Yang

Yan³

et al. 2022

PGPM

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Purpose Osteoporotic vertebral compression fracture (OVCF) is a common disease in the elderly, and genetic factors play a key role in its occurrence. The present study was conducted to investigate the association between interleukin-6 ( IL-6 ) and the transforming growth factor ( TGF-β ) gene polymorphisms and the occurrence of thoracolumbar OVCF. Patients and Methods This case–control study recruited 146 patients with OVCF and 144 osteoporosis patients as the control group. Genotypes of the IL-6 rs1800796 and TGF-β rs1982073 were analyzed by sequencing. Genotype distribution and allelic frequencies were investigated by the χ 2 test. Odds ratios (OR) and 95% confidence intervals (CI) evaluated the relationship of IL-6 or TGF-β polymorphism and OVCF susceptibility. Results Allele G and genotype GG of IL-6 rs1800796 was more frequent in patients with OVCF (40.07% vs.28.47%; 19.18% vs.7.64%) compared with controls. GG genotype (OR=3.394, 95% CI=1.560–7.385, P < 0.001) and G allele (OR=1.680, 95% CI=1.187–2.376, P < 0.001) of IL-6 rs1800796 was significantly associated with increased risk of OVCF. What is more, CT and TT genotypes (41.78 vs.51.39; 19.86 vs.26.39) and allele T (40.75 vs 52.08) of TGF-β rs1982073 were less frequent in OVCFs, more common in controls and protective against OVCF risk (OR=0.436, 95% CI=0.228–0.835, P = 0.012; OR=0.615, 95% CI=0.443–0.855, P = 0.004). Conclusion Our results suggest that the G allele and GG genotype of IL-6 rs1800796 may contribute to increased susceptibility to OVCF in elderly Chinese. In contrast, CT and TT genotypes and the T allele of TGF-β rs1982073 may contribute to lower susceptibility of OVCF.

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Changes in macrophage and inflammatory cytokine expressions during fracture healing in an ovariectomized mice model

Cited by 12 publications

References 49 publications

The role of macrophages in fracture healing: a narrative review of the recent updates and therapeutic perspectives

The role of macrophages in fracture healing: a narrative review of the recent updates and therapeutic perspectives

Regulon active landscape reveals cell development and functional state changes of human primary osteoblasts in vivo

Association of IL-6 and TGF-β Gene Polymorphisms with the Risk of Thoracolumbar Osteoporotic Vertebral Compression Fractures

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