Cellular and morphological aspects of fibrodysplasia ossificans progressiva

Martelli, Anderson; Santos, Arnaldo Rodrigues

doi:10.4161/org.29206

Cited by 18 publications

(13 citation statements)

References 72 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Bone graft defect is the most common complication among patients undergoing bone grafting, resulting in the increasing risk of infection, delayed bone union, fracture or disability (1)(2)(3). A series of cellular repair programs are involved in bone tissue defects, such as the infiltration of host reparative cells into the damaged sites, the proliferation and differentiation of the cells, and the signal transduction of extracellular molecules (4)(5)(6). Macrophages secrete a wide range of inflammatory and chemotactic mediators, including tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6 and IL-17, which can further initiate the loss of bone mesenchymal stem cells (BMSCs) and suppress bone formation (7).…”

Section: Introductionmentioning

confidence: 99%

Puerarin improves graft bone defect through microRNA‑155‑3p‑mediated p53/TNF‑α/STAT1 signaling pathway

et al. 2020

View full text Add to dashboard Cite

Bone graft defects may lead to dysfunction of bone regeneration and metabolic disorders of bone mesenchymal stem cells (BMScs). Puerarin has demonstrated pharmacological activities in the treatment of human metabolic diseases. The purpose of the present study was to investigate the role of puerarin and to explore its possible protective mechanism of action in rats with bone grafts. A bone graft rat model was established using bone grafting surgery and the rats received puerarin or PBS. Reverse transcription-quantitative PcR, western blot, TUNEL, immunofluorescence and immunohistochemistry assays were used to analyze the beneficial effects of puerarin on bone repair. The results demonstrated that puerarin effectively ameliorated pathological graft bone defects, decreased bone loss and apoptosis of BMScs, promoted BMSc proliferation and differentiation, and increased bone mass and the parameters of bone formation in rats with bone grafts. Puerarin decreased the levels of pro-inflammatory cytokines [tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-17A, IL-6 and transforming growth factor (TGF)-β1] and increased the levels of anti-inflammatory cytokines (IL-2 and IL-10) in the serum compared with the PBS group. Puerarin treatment was associated with lower serum alanine transaminase, glutamic oxaloacetic transaminase, γ-glutamyl transferase, alkaline phosphatase, direct bilirubin and total bilirubin levels compared with those in the PBS group in experimental rats. The expression of microRNA-155-3p (miR-155-3p) was upregulated, whereas that of p53, TNF-α and signal transducer and activator of transcription (STAT)1 was downregulated in BMSc cultures of puerarin-treated rats.In vitro assay demonstrated that knockdown of miR-155-3p increased p53, TNF-α and STAT1 expression in BMScs, and blocked puerarin-regulated p53/TNF-α/STAT1 signaling. Most importantly, miR-155-3p knockdown inhibited puerarin-regulated apoptosis, proliferation and differentiation of BMScs. Moreover, the results demonstrated that puerarin regulated vascular endothelial growth factor expression via the miR-155-3p signaling pathway. In conclusion, the results of the present study demonstrated that the upregulation of miR-155-3p induced by puerarin promoted BMSc differentiation and bone formation and increased bone mass in rats with bone grafts, thereby supporting the potential application of puerarin in the prevention of bone graft defects.

show abstract

Section: Introductionmentioning

confidence: 99%

Puerarin improves graft bone defect through microRNA‑155‑3p‑mediated p53/TNF‑α/STAT1 signaling pathway

et al. 2020

View full text Add to dashboard Cite

show abstract

“…Les ossifications extra squelettiques concernent les muscles à insertions squelettiques, les fascias, les aponévroses, les tendons et les ligaments. Elles ont toutes les caractéristiques de l'os normal dans la FOP : les organisations corticales et trabéculaires matures, la frontière corticale-endostéale bien définie qui entoure les canaux médullaires et la tunnelisation métaphysaire montrent la maturité de l'os formé [5].…”

Section: Discussionunclassified

Heterotopic ossifications responsible for early functional impairment in a patient with fibrodysplasia ossificans progressiva

Ranaivoarison¹,

Rakotomalala²,

Andrianjafison³

et al. 2017

Batna J Med Sci

View full text Add to dashboard Cite

La fibrodysplasie ossifiante progressive (FOP) ou maladie de Munchmeyer est une maladie génétique très rare, caractérisée par une ossification hétérotopique endochondrale des muscles à insertion squelettiques et d’autres tissus conjonctifs. L’enraidissement total en est le stade le plus avancé. Nous rapportons le cas d’une jeune fille de 14 ans déjà au stade de blocage complet des membres inférieurs.

show abstract

“…However, there is also a debate as to whether aberrant BMP signalling is solely responsible for HO in FOP (Kan et al, 2018). Given the role of Hedgehog (Hh) signalling, mediated predominantly via Indian Hh in normal osteogenesis, especially the differentiation of chondrocytes during endochondral ossification (Martelli and Santos, 2014;Lai and Mitchell, 2005;St-Jacques et al, 1999;Long et al, 2004), it is plausible that this pathway may also contribute to HO in FOP, which has yet to be explored in detail. Similarly, the Wnt/β-catenin signalling pathway, which is thought to influence the differentiation and function of mesenchymal stem cells, chondrocytes, osteoblasts and osteoclasts during normal bone formation, may also have a role (Regard et al, 2012).…”

Section: Future Directionsmentioning

confidence: 99%

Fibrodysplasia ossificans progressiva: current concepts from bench to bedside

Kaliya-Perumal

Carney

Ingham

2020

Disease Models &Amp; Mechanisms

View full text Add to dashboard Cite

Heterotopic ossification (HO) is a disorder characterised by the formation of ectopic bone in soft tissue. Acquired HO typically occurs in response to trauma and is relatively common, yet its aetiology remains poorly understood. Genetic forms, by contrast, are very rare, but provide insights into the mechanisms of HO pathobiology. Fibrodysplasia ossificans progressiva (FOP) is the most debilitating form of HO. All patients reported to date carry heterozygous gain-of-function mutations in the gene encoding activin A receptor type I (ACVR1). These mutations cause dysregulated bone morphogenetic protein (BMP) signalling, leading to HO at extraskeletal sites including, but not limited to, muscles, ligaments, tendons and fascia. Ever since the identification of the causative gene, developing a cure for FOP has been a focus of investigation, and studies have decoded the pathophysiology at the molecular and cellular levels, and explored novel management strategies. Based on the established role of BMP signalling throughout HO in FOP, therapeutic modalities that target multiple levels of the signalling cascade have been designed, and some drugs have entered clinical trials, holding out hope of a cure. A potential role of other signalling pathways that could influence the dysregulated BMP signalling and present alternative therapeutic targets remains a matter of debate. Here, we review the recent FOP literature, including pathophysiology, clinical aspects, animal models and current management strategies. We also consider how this research can inform our understanding of other types of HO and highlight some of the remaining knowledge gaps.

show abstract

Cellular and morphological aspects of fibrodysplasia ossificans progressiva

Cited by 18 publications

References 72 publications

Puerarin improves graft bone defect through microRNA‑155‑3p‑mediated p53/TNF‑α/STAT1 signaling pathway

Puerarin improves graft bone defect through microRNA‑155‑3p‑mediated p53/TNF‑α/STAT1 signaling pathway

Heterotopic ossifications responsible for early functional impairment in a patient with fibrodysplasia ossificans progressiva

Fibrodysplasia ossificans progressiva: current concepts from bench to bedside

Contact Info

Product

Resources

About