Heterotopic Ossification: Clinical Features, Basic Researches, and Mechanical Stimulations

Xu, Yili; Mei, Huang; He, Wenzhen; He, Chen; Chen, Kaixuan; Hou, Jing; Huang, Min; Jiao, Yurui; Liu, Ran; Zou, Nanyu; Liu, Ling; Li, Changjun

doi:10.3389/fcell.2022.770931

Cited by 31 publications

(51 citation statements)

References 133 publications

(169 reference statements)

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“… 141 – 144 The unique cellular source is one of the most notable differences between pathological HO and normal osteogenesis. 145 Evidence suggests that the local activities of macrophages, monocytes, and other cells at prospective HO sites result in significant increases in inflammatory cytokine levels. 146 These factors cause the mobilization and recruitment of certain stem cell populations 147 as well as the local activation of pro-skeletogenic signaling processes, 148 leading to the activation of chondrogenesis and osteogenesis and the accumulation of ectopic bone tissue.…”

Section: Introductionmentioning

confidence: 99%

Single-cell RNA sequencing in orthopedic research

et al. 2023

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Although previous RNA sequencing methods have been widely used in orthopedic research and have provided ideas for therapeutic strategies, the specific mechanisms of some orthopedic disorders, including osteoarthritis, lumbar disc herniation, rheumatoid arthritis, fractures, tendon injuries, spinal cord injury, heterotopic ossification, and osteosarcoma, require further elucidation. The emergence of the single-cell RNA sequencing (scRNA-seq) technique has introduced a new era of research on these topics, as this method provides information regarding cellular heterogeneity, new cell subtypes, functions of novel subclusters, potential molecular mechanisms, cell-fate transitions, and cell‒cell interactions that are involved in the development of orthopedic diseases. Here, we summarize the cell subpopulations, genes, and underlying mechanisms involved in the development of orthopedic diseases identified by scRNA-seq, improving our understanding of the pathology of these diseases and providing new insights into therapeutic approaches.

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Section: Introductionmentioning

confidence: 99%

Single-cell RNA sequencing in orthopedic research

et al. 2023

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“…Typical clinical symptoms in the early phases are such as localized pain, tenderness, and swelling. At later stages, a limited range of motion (ROM) may affect the joint, resulting in complete ankylosis in the most severe cases [ 2 ].…”

Section: Introductionmentioning

confidence: 99%

“…The mTOR is a nutrient sensor and a controller of protein synthesis. The mTOR protein complex-1 (mTORC1) influences cell growth, survival, and proliferation in response to oxygen level, energy status, growth factors, amino acids level [ 65 ] or mechanical stimulation [ 2 ]. Other factors such as HH and WNT/β-catenin pathways responsible for skeletal maturation and regeneration are also affected by genetic and acquired HO [ 66 ].…”

Section: Introductionmentioning

confidence: 99%

The role of miRNA and lncRNA in heterotopic ossification pathogenesis

et al. 2022

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Heterotopic ossification (HO) is the formation of bone in non-osseous tissues, such as skeletal muscles. The HO could have a genetic or a non-genetic (acquired) background, that is, it could be caused by musculoskeletal trauma, such as burns, fractures, joint arthroplasty (traumatic HO), or cerebral or spinal insult (neurogenetic HO). HO formation is caused by the differentiation of stem or progenitor cells induced by local or systemic imbalances. The main factors described so far in HO induction are TGFβ1, BMPs, activin A, oncostatin M, substance P, neurotrophin-3, and WNT. In addition, dysregulation of noncoding RNAs, such as microRNA or long noncoding RNA, homeostasis may play an important role in the development of HO. For example, decreased expression of miRNA-630, which is responsible for the endothelial–mesenchymal transition, was observed in HO patients. The reduced level of miRNA-421 in patients with humeral fracture was shown to be associated with overexpression of BMP2 and a higher rate of HO occurrence. Down-regulation of miRNA-203 increased the expression of runt-related transcription factor 2 (RUNX2), a crucial regulator of osteoblast differentiation. Thus, understanding the various functions of noncoding RNAs can reveal potential targets for the prevention or treatment of HO.

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“…Heterotopic ossification can be either congenital or acquired. The latter is usually related to trauma (2). Patients with early heterotopic ossification have obvious local swelling and pain, the range of motion of the joints gradually narrows, and movement is restricted; in the late stage, due to the loss of more soft tissue and the formation of bone tissue, the joints may even lose the ability to move (3).…”

Section: Introductionmentioning

confidence: 99%

A Network Pharmacology Study: Reveal the Mechanisms of Palovarotene Against Heterotopic Ossification

et al. 2022

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Heterotopic ossification (HO) occurs when bone forms within non-ossifying tissues, such as in muscle. Palovarotene, an activator of retinoic acid receptor γ (RAR-γ), has been shown to inhibit the formation of ectopic bone in HO model mice, but its specific mechanism of action remains unclear. This study will explore the target and molecular mechanism of Palovarotene's action on HO by network pharmacology study. We collected the relevant targets of Palovarotene and HO from the database, obtained the potential targets of Palovarotene acting on HO through Venn analysis, and constructed the protein-protein interaction (PPI) network. Then, Gene Ontology (GO) and KEGG (Kyoto Encyclopedia of Genes and Genomes) enrichment Analysis and Module-based Network Analysis were performed for potential targets, and in addition, PPI Network Topology Analysis and Gene-Phenotype Correlation Analysis were performed. The results suggested that MAPK1, MDM2, and other targets as well as P53 signaling pathway and PI3K–Akt signaling pathway may be closely related to Palovarotene treatment of HO. We carried out verification experiments to confirm our finding, alkaline phosphatase and alizarin red staining in vitro and Micro-CT as well as hematoxylin-eosin staining in vivo were performed to verify treatment for HO of Palovarotene, reverse transcription polymerase chain reaction was also used to explore the transcription changes of MAPK1, MDM2, and osteogenic genes. This study systematically elucidated the possible mechanism of Palovarotene in the treatment of HO through network pharmacology study, revealing a new direction for the further application of Palovarotene in the treatment of HO.

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Heterotopic Ossification: Clinical Features, Basic Researches, and Mechanical Stimulations

Cited by 31 publications

References 133 publications

Single-cell RNA sequencing in orthopedic research

Single-cell RNA sequencing in orthopedic research

The role of miRNA and lncRNA in heterotopic ossification pathogenesis

A Network Pharmacology Study: Reveal the Mechanisms of Palovarotene Against Heterotopic Ossification

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