1.Molecular biological mechanism of acquired heterotopic ossification
Yang XIONG ; Shibo ZHOU ; Xing YU ; Lianyong BI ; Jizhou YANG ; Fengxian WANG ; Yi QU ; Yongdong YANG ; Dingyan ZHAO ; He ZHAO ; Ziye QIU ; Guozheng JIANG
Chinese Journal of Tissue Engineering Research 2024;28(30):4881-4888
BACKGROUND:Heterotopic ossification is a dynamic growth process.Diverse heterotopic ossification subtypes have diverse etiologies or induction factors,but they exhibit a similar clinical process in the intermediate and later phases of the disease.Acquired heterotopic ossification produced by trauma and other circumstances has a high incidence. OBJECTIVE:To summarize the molecular biological mechanisms linked to the occurrence and progression of acquired heterotopic ossification in recent years. METHODS:The keywords"molecular biology,heterotopic ossification,mechanisms"were searched in CNKI,Wanfang,PubMed,Embase,Web of Science,and Google Scholar databases for articles published from January 2016 to August 2022.Supplementary searches were conducted based on the obtained articles.After the collected literature was screened,131 articles were finally included and summarized. RESULTS AND CONCLUSION:(1)The occurrence and development of acquired heterotopic ossification is a dynamic process with certain concealment,making diagnosis and treatment of the disease difficult.(2)By reviewing relevant literature,it was found that acquired heterotopic ossification involves signaling pathways such as bone morphogenetic protein,transforming growth factor-β,Hedgehog,Wnt,and mTOR,as well as core factors such as Runx-2,vascular endothelial growth factor,hypoxia-inducing factor,fibroblast growth factor,and Sox9.The core mechanism may be the interaction between different signaling pathways,affecting the body's osteoblast precursor cells,osteoblast microenvironment,and related cytokines,thereby affecting the body's bone metabolism and leading to the occurrence of acquired heterotopic ossification.(3)In the future,it is possible to take the heterotopic ossification-related single-cell osteogenic homeostasis as the research direction,take the osteoblast precursor cells-osteogenic microenvironment-signaling pathways and cytokines as the research elements,explore the characteristics of each element under different temporal and spatial conditions,compare the similarities and differences of the osteogenic homeostasis of different types and individuals,observe the regulatory mechanism of the molecular signaling network of heterotopic ossification from a holistic perspective.It is beneficial to the exploration of new methods for the future clinical prevention and treatment of heterotopic ossification.(4)Meanwhile,the treatment methods represented by traditional Chinese medicine and targeted therapy have become research hotspots in recent years.How to link traditional Chinese medicine with the osteogenic homeostasis in the body and combine it with targeted therapy is also one of the future research directions.(5)At present,the research on acquired heterotopic ossification is still limited to basic experimental research and the clinical prevention and treatment methods still have defects such as uncertain efficacy and obvious side effects.The safety and effectiveness of relevant targeted prevention and treatment drugs in clinical application still need to be verified.Future research should focus on clinical prevention and treatment based on basic experimental research combined with the mechanism of occurrence and development.
2.Therapeutic Effects of Spider Toxin Oral Ulcer Powder on Oral Ulcer Model Rats and Its Mechanism Study
Guozheng XING ; Changna WANG ; Xutong TIAN ; Jiamei TANG ; Yujie ZHANG ; Xiaoqiang QIAO ; Chengyan ZHOU
China Pharmacy 2019;30(8):1043-1048
OBJECTIVE: To study therapeutic effects of Spider toxin oral ulcer powder on recurrent aphthous ulcer (RAU) model rats and its mechanism. METHODS: In vitro antimicrobial activity of the powder was determined by disk diffusion method. 50 healthy SD rats were randomly divided into normal group, model group, positive group (Guilin watermelon frost, 100 mg/kg) and oral ulcer powder high-dose and low-dose groups (70, 35 mg/kg), with 10 rats in each group. Except for normal group, RAU model was established in the right oral submucosa of rats in other groups by acetic acid method. After modeling, administration groups were smeared with corresponding drugs on ulcers for 3 days. Normal group and model group were not treated. The ulcer surface of rats was observed and the ulcer area was measured on the 1st and 3rd days after administration. The morphological changes of ulcer tissues were observed. The serum levels of SOD, MDA, GSH, TNF-α, IL-1, IL-6 and IFN-γ were detected. The protein expressions of MMP-9, NF-κB, Caspase-3 and PARP in ulcer tissues of rats were detected by immunohistochemistry. RESULTS: The oral ulcer powder showed obvious in vitro bacteriostasis effect. Compared with blank group, oral ulcer and histopathological changes were obvious in model group; serum levels of TNF-α, IL-1, IL-6 and MDA were increased significantly, while the levels of IFN-γ, SOD and GSH were decreased significantly (P<0.01); the expression of MMP-9, NF-κB, Caspase-3 and PARP in ulcer tissue were increased significantly (P<0.05 or P<0.01). Compared with model group, the ulcer area of rats in each dosage group was significantly reduced (P<0.05 or P<0.01) or nearly healed, the pathological changes of tissue were significantly alleviated; serum levels of MDA, TNF-α, IL-1 and IL-6 were decreased significantly, while the levels of SOD, GSH and IFN-γ were increased significantly (P<0.05 or P<0.01); the expression of MMP-9, NF-κB, Caspase-3 and PARP in ulcer tissue were decreased significantly (P<0.01). CONCLUSIONS: Spider toxin oral ulcer powder shows strong bacteriostasis, detumescence and repair effects, and has obvious therapeutic effect on RAU model rats. Its mechanism may be related to reducing the level of inflammatory factors, mediating the expression of apoptotic factors and regulating immune imbalance.