Yuan Li, Chenglong Li, Wensheng Zhang, Shiyong Le, Jiongjiong Zhou, Bijun Luo, Pusheng Xie, Bo Yan
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引用次数: 0
Abstract
Heterotopic ossification (HO) affects millions of people worldwide. TGF-β/Smad signaling pathway plays an essential role in HO of the Achilles tendon. Recent studies have found that Theaflavin can regulate the TGF-β/Smad signaling pathway, suggesting Theaflavin may have a positive effect on HO. In this study, we aimed to study the effects of Theaflavin on preventing endochondral differentiation of Tendon-derived stem cells (TDSCs) and the HO process after the achilles tendon injury model. Here, we investigated the role of Theaflavin in a mouse model of Achilles tendon heterotopic ossification. In addition, we use TDSCs to explore the molecular mechanism of Theaflavin affecting HO. Our data showed that Theaflavin can inhibit HO of the Achilles tendon and significantly reduce the volume of mature bone tissues. SOX9 and RUNX2 were decreased significantly after Theaflavin administration. Experiments showed Theaflavin inhibited TGF-β/Smad signaling pathway during chondrogenic differentiation and osteogenic differentiation of TDSCs. Surface Plasmon Resonance Assay and Molecular docking simulation showed that a direct molecular interaction between Theaflavin and TβRI (a membrane receptor of TGF-βs). Meanwhile, Cellular Thermal Shift Assay showed Theaflavin bonded and thermally stabilized TβRI significantly. Moreover, WB and IHC displayed Theaflavin also exhibited inhibitory effects on TβRI phosphorylation. In summary, Our findings demonstrated that TF inhibited HO by down-regulating the TGF-β/Smad signal pathway, and this effect may attributed to TF binded directly to TβRI and prevented its phosphorylation.
期刊介绍：
Biochemical Pharmacology publishes original research findings, Commentaries and review articles related to the elucidation of cellular and tissue function(s) at the biochemical and molecular levels, the modification of cellular phenotype(s) by genetic, transcriptional/translational or drug/compound-induced modifications, as well as the pharmacodynamics and pharmacokinetics of xenobiotics and drugs, the latter including both small molecules and biologics.
The journal''s target audience includes scientists engaged in the identification and study of the mechanisms of action of xenobiotics, biologics and drugs and in the drug discovery and development process.
All areas of cellular biology and cellular, tissue/organ and whole animal pharmacology fall within the scope of the journal. Drug classes covered include anti-infectives, anti-inflammatory agents, chemotherapeutics, cardiovascular, endocrinological, immunological, metabolic, neurological and psychiatric drugs, as well as research on drug metabolism and kinetics. While medicinal chemistry is a topic of complimentary interest, manuscripts in this area must contain sufficient biological data to characterize pharmacologically the compounds reported. Submissions describing work focused predominately on chemical synthesis and molecular modeling will not be considered for review.
While particular emphasis is placed on reporting the results of molecular and biochemical studies, research involving the use of tissue and animal models of human pathophysiology and toxicology is of interest to the extent that it helps define drug mechanisms of action, safety and efficacy.
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