2.Research progress of chondrocyte mechanotransduction mediated by TRPV4 and PIEZOs.
Qiang ZHANG ; K Tawiah GODFRED ; Yanjun ZHANG ; Xiaochun WEI ; Weiyi CHEN ; Quanyou ZHANG
Journal of Biomedical Engineering 2023;40(4):638-644
Mechanical signal transduction are crucial for chondrocyte in response to mechanical cues during the growth, development and osteoarthritis (OA) of articular cartilage. Extracellular matrix (ECM) turnover regulates the matrix mechanical microenvironment of chondrocytes. Thus, understanding the mechanotransduction mechanisms during chondrocyte sensing the matrix mechanical microenvironment can develop effective targeted therapy for OA. In recent decades, growing evidences are rapidly advancing our understanding of the mechanical force-dependent cartilage remodeling and injury responses mediated by TRPV4 and PIEZOs. In this review, we highlighted the mechanosensing mechanism mediated by TRPV4 and PIEZOs during chondrocytes sensing mechanical microenvironment of the ECM. Additionally, the latest progress in the regulation of OA by inflammatory signals mediated by TRPV4 and PIEZOs was also introduced. These recent insights provide the potential mechanotheraputic strategies to target these channels and prevent cartilage degeneration associated with OA. This review will shed light on the pathogenesis of articular cartilage, searching clinical targeted therapies, and designing cell-induced biomaterials.
Chondrocytes
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TRPV Cation Channels
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Mechanotransduction, Cellular
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Biocompatible Materials
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Cartilage, Articular
3.ASIC2 Synergizes with TRPV1 in the Mechano-Electrical Transduction of Arterial Baroreceptors.
Xiaodong YAN ; Sitao ZHANG ; Haiyan ZHAO ; Ping LIU ; Haixia HUANG ; Weizhen NIU ; Wei WANG ; Chen ZHANG
Neuroscience Bulletin 2021;37(10):1381-1396
Mechanosensitive ion channels (MSCs) are key molecules in the mechano-electrical transduction of arterial baroreceptors. Among them, acid-sensing ion channel 2 (ASIC2) and transient receptor potential vanilloid subfamily member 1 (TRPV1) have been studied extensively and documented to play important roles. In this study, experiments using aortic arch-aortic nerve preparations isolated from rats revealed that both ASIC2 and TRPV1 are functionally necessary, as blocking either abrogated nearly all pressure-dependent neural discharge. However, whether ASIC2 and TRPV1 work in coordination remained unclear. So we carried out cell-attached patch-clamp recordings in HEK293T cells co-expressing ASIC2 and TRPV1 and found that inhibition of ASIC2 completely blocked stretch-activated currents while inhibition of TRPV1 only partially blocked these currents. Immunofluorescence staining of aortic arch-aortic adventitia from rats showed that ASIC2 and TRPV1 are co-localized in the aortic nerve endings, and co-immunoprecipitation assays confirmed that the two proteins form a compact complex in HEK293T cells and in baroreceptors. Moreover, protein modeling analysis, exogenous co-immunoprecipitation assays, and biotin pull-down assays indicated that ASIC2 and TRPV1 interact directly. In summary, our research suggests that ASIC2 and TRPV1 form a compact complex and function synergistically in the mechano-electrical transduction of arterial baroreceptors. The model of synergism between MSCs may have important biological significance beyond ASIC2 and TRPV1.
Acid Sensing Ion Channels/physiology*
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Animals
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HEK293 Cells
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Humans
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Pressoreceptors/physiology*
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Rats
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TRPV Cation Channels/physiology*
4.Transient Receptor Potential Vanilloid 1-Immunoreactive Innervation Increases in Fractured Rat Femur.
Yuya KAWARAI ; Miyako SUZUKI ; Kensuke YOSHINO ; Gen INOUE ; Sumihisa ORITA ; Kazuyo YAMAUCHI ; Yasuchika AOKI ; Tetsuhiro ISHIKAWA ; Masayuki MIYAGI ; Hiroto KAMODA ; Go KUBOTA ; Yoshihiro SAKUMA ; Yasuhiro OIKAWA ; Kazuhide INAGE ; Takeshi SAINOH ; Jun SATO ; Junichi NAKAMURA ; Masashi TAKASO ; Tomoaki TOYONE ; Kazuhisa TAKAHASHI ; Seiji OHTORI
Yonsei Medical Journal 2014;55(1):185-190
PURPOSE: Pain from vertebral or femoral neck fractures is a particularly important problem in clinical orthopaedics. Transient receptor potential vanilloid 1 (TRPV1) is a ligand-gated nonselective cation channel, and there are recent reports on an association between bone pain and TRPV1. However, an increase in TRPV1 activity has not been reported following femoral fracture. MATERIALS AND METHODS: We applied a neurotracer [Fluoro-gold (FG)] onto femur to detect dorsal root ganglia (DRGs) innervating the cortex of the femur in 30 Sprague Dawley rats. Seven days after application, a closed mid-diaphyseal fracture of the femur was performed. FG labeled TRPV1-immunoreactive (ir) DRGs innervating the femur were examined in nonfractured controls, and 3 days, 1 week, 2 weeks, and 4 weeks after fracture. We evaluated bone healing of the femur and compared the ratio of TRPV1-ir DRG neurons innervating the femur at the time points. RESULTS: Four weeks after fracture, complete bone union was observed. There was no significant difference in the ratio of FG labeled DRG neurons to total DRG neurons at each time point. The percentages of TRPV1-ir neurons in DRGs innervating the femur at 3 days and 1 week after fracture were significantly higher than those in control, 2 weeks, and 4 weeks after fracture (p<0.05). CONCLUSION: Fracture induced an increase of TRPV1-ir neurons in DRGs innervating the fractured femur within 3 days, and decreased during bone healing over 4 weeks. These findings show that TRPV1 may play a role in sensory sensation of bone fracture pain.
Animals
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Female
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Femur/*innervation/*metabolism
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Immunohistochemistry
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Rats
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Rats, Sprague-Dawley
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TRPV Cation Channels/*metabolism
5.Human skeletal dysplasia caused by a constitutive activated transient receptor potential vanilloid 4 (TRPV4) cation channel mutation.
Sang Sun KANG ; Sung Hwa SHIN ; Chung Kyoon AUH ; Jaesun CHUN
Experimental & Molecular Medicine 2012;44(12):707-722
The transient receptor potential vanilloid 4 (TRPV4) cation channel, a member of the TRP vanilloid subfamily, is expressed in a broad range of tissues where it participates in the generation of Ca2+ signals and/or depolarization of the membrane potential. Regulation of TRPV4 abundance at the cell surface is critical for osmo- and mechanotransduction. Defects in TRPV4 are the cause of several human diseases, including brachyolmia type 3 (MIM:113500) (also known as brachyrachia or spondylometaphyseal dysplasia Kozlowski type [MIM:118452]), and metatropic dysplasia (MIM:156530) (also called metatropic dwarfism or parastremmatic dwarfism [MIM:168400]). These bone dysplasia mutants are characterized by severe dwarfism, kyphoscoliosis, distortion and bowing of the extremities, and contractures of the large joints. These diseases are characterized by a combination of decreased bone density, bowing of the long bones, platyspondyly, and striking irregularities of endochondral ossification with areas of calcific stippling and streaking in radiolucent epiphyses, metaphyses, and apophyses. In this review, we discuss the potential effect of the mutation on the regulation of TRPV4 functions, which are related to human diseases through deviated function. In particular, we emphasize how the constitutive active TRPV4 mutant affects endochondral ossification with a reduced number of hypertrophic chondrocytes and the presence of cartilage islands within the zone of primary mineralization. In addition, we summarize current knowledge about the role of TRPV4 in the pathogenesis of several diseases.
Humans
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*Mutation
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Osteochondrodysplasias/*genetics
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Osteogenesis/genetics
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TRPV Cation Channels/chemistry/*genetics/metabolism
6.Anti-inflammatory: effect mechanism of warming-dredging in moxibustion.
Jin-Feng JIANG ; Ling-Ling WANG ; Xu BIN ; Hu LING ; Xiao-Ge SONG ; Huan-Gan WU
Chinese Acupuncture & Moxibustion 2013;33(9):860-864
The universality of anti-inflammation in moxibustion is analyzed in this article from its adaptation disease and ancient documentary records. The specificity of anti-inflammation in moxibustion is pointed out from its disease series research and scientific fact that moxibustion could be used for heat syndrome. The integrity of anti-inflammation in moxibustion is explained by series research result that four basic circulations of moxibustion for chronic inflammation are all effective. The two-way characteristic of moxibustion anti-inflammation is explained from the fact that moxibustion has regulation function both for excess and insufficiency of inflammation to demonstrate the effect mechanism of warming-dredging in moxibustion lies in its anti-inflammation. At last, the relevant possible mechanism between moxibustion anti-inflammation and transient receptor potential vanilloid (TRPV) is proposed. The effect mechanism of warming-dredging in moxibustion lies in anti-inflammation, which could provide theoretic basis for prevention and treatment of moxibustion for serious diseases.
Animals
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Humans
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Inflammation
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genetics
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immunology
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therapy
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Moxibustion
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instrumentation
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methods
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TRPV Cation Channels
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genetics
;
immunology
7.Research progress of TRPV4 and cerebral ischemic reperfusion injury.
Hao DING ; Ye-Xin LIN ; Qi-Wen SHEN ; Zhi PAN ; Zhen-Chao WANG ; Lei CHEN
Acta Physiologica Sinica 2015;67(5):527-532
Transient receptor potential vanilloid 4 (TRPV4) channel is a member of transient receptor potential superfamily. TRPV4 is selectively permeable to calcium. Activation of the TRPV4 channel induces an increase in intracellular calcium concentration and plays an important role under physiological and pathological conditions. Especially, there is evidence showing that TRPV4 is involved in cerebral ischemic reperfusion injury. The present paper reviewed some research progress about the role of TRPV4 in cerebral ischemic reperfusion injury.
Brain Ischemia
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Calcium
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physiology
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Humans
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Reperfusion Injury
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TRPV Cation Channels
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physiology
8.Study on relations between transient receptor potential vanilloid 1 and pungent property of traditional Chinese medicines.
Xing WANG ; Yan-Ling ZHANG ; Yun WANG ; Zhen-Zhen REN ; Hong-Juan BAO ; Yan-Jiang QIAO
China Journal of Chinese Materia Medica 2014;39(13):2422-2427
The five-flavor theory of traditional Chinese medicines (TCM) and the flavor efficacy generation mechanism has long been focuses and difficulties in studies on traditional Chinese medicinal properties. In this paper, by using the pharmacophore-based virtual screening technique, the authors discussed the relations between the pungent property and transient receptor potential vanilloid 1 (TRPV1) by studying the TCM components' role in regulating TRPV1 ion channel. The results showed that the matching relationship between TRPV1 agonist pharmacophore model and TCM chemical components could identify the active ingredients from pungent herbs. Therefore, the authors proposed that TRPV1 is one of the potential targets for efficient pungent herbs. The pungent property of TCMs is decided by its chemical components, and consistent with the inherited and additive characteristics.
Drugs, Chinese Herbal
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chemistry
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pharmacology
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Humans
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Smell
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TRPV Cation Channels
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antagonists & inhibitors
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metabolism
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Taste
9.The effects of anthocyanin on chronic inflammatory pain induced by complete Freund's adjuvant and its mechanism.
Jing WANG ; Ze-Feng CHEN ; Chun-Xia HE ; Li-Li WANG ; Jia-Hui ZHENG ; Hao ZHANG ; Zhan-Lei WANG ; Ya-Ping LU
Chinese Journal of Applied Physiology 2018;34(5):476-480
OBJECTIVE:
To investigate the effects and mechanisms of anthocyanin from Ligustrum vicaryi on chronic inflammatory pain induced by complete Freund's adjuvant.
METHODS:
Thirty male SD rats were randomly divided into three groups (=10):normal saline control group (NS), chronic inflammatory pain model group(Mod, injected with complete Freund's adjuvant(CFA) 100 μl to the left hind leg), anthocyanin treatment group(Ant, dosed with anthocyanins (90 m), mechanical pain threshold (MPT), and left toe volume in each group were measured before modeling and 1,3,5,7,9,11,13 days after operation. Antioxidant indexes in serum were mensurated by spectrophotometer, and the total capsaicin receptor (TRPV1) and phosphorylated capsaicin receptor (p-TRPV1) in hippocampus were detected by Western blot.
RESULTS:
In comparison with controls, HPT and MPT were improved (<0.05),toe swelling was reduced(<0.05), the serum level of SOD was increased (<0.01), while the levels of MDA and NO were decreased (<0.05), the ratio of P-TRPV1/TRPV1 protein was depressed in Mod rat hippocampal region treated with anthocyanin.
CONCLUSIONS
The results show that anthocyanins has an analgesic effect on chronic inflammatory pain induced by CFA, and its mechanism may be related to the improvement of antioxidant capacity and the reduction of TRPV1 phosphorylation.
Animals
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Anthocyanins
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Freund's Adjuvant
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Inflammation
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Male
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Pain
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Rats
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Rats, Sprague-Dawley
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TRPV Cation Channels
10.Understand spiciness: mechanism of TRPV1 channel activation by capsaicin.
Protein & Cell 2017;8(3):169-177
Capsaicin in chili peppers bestows the sensation of spiciness. Since the discovery of its receptor, transient receptor potential vanilloid 1 (TRPV1) ion channel, how capsaicin activates this channel has been under extensive investigation using a variety of experimental techniques including mutagenesis, patch-clamp recording, crystallography, cryo-electron microscopy, computational docking and molecular dynamic simulation. A framework of how capsaicin binds and activates TRPV1 has started to merge: capsaicin binds to a pocket formed by the channel's transmembrane segments, where it takes a "tail-up, head-down" configuration. Binding is mediated by both hydrogen bonds and van der Waals interactions. Upon binding, capsaicin stabilizes the open state of TRPV1 by "pull-and-contact" with the S4-S5 linker. Understanding the ligand-host interaction will greatly facilitate pharmaceutical efforts to develop novel analgesics targeting TRPV1.
Binding Sites
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Capsaicin
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chemistry
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pharmacokinetics
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Humans
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Hydrogen Bonding
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Protein Binding
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TRPV Cation Channels
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chemistry
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genetics
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metabolism