Humans ; Ion Channels ; Pain ; Pressure ; TRPM Cation Channels ; TRPV Cation Channels ; Temperature

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 ; TRPV Cation Channels ; Mechanotransduction, Cellular ; Biocompatible Materials ; Cartilage, Articular

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* ; Animals ; HEK293 Cells ; Humans ; Pressoreceptors/physiology* ; Rats ; TRPV Cation Channels/physiology*

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 ; *Mutation ; Osteochondrodysplasias/*genetics ; Osteogenesis/genetics ; TRPV Cation Channels/chemistry/*genetics/metabolism

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 ; chemistry ; pharmacology ; Humans ; Smell ; TRPV Cation Channels ; antagonists & inhibitors ; metabolism ; Taste

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 ; Female ; Femur/*innervation/*metabolism ; Immunohistochemistry ; Rats ; Rats, Sprague-Dawley ; TRPV Cation Channels/*metabolism

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 ; Humans ; Inflammation ; genetics ; immunology ; therapy ; Moxibustion ; instrumentation ; methods ; TRPV Cation Channels ; genetics ; immunology

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 ; Calcium ; physiology ; Humans ; Reperfusion Injury ; TRPV Cation Channels ; physiology

OBJECTIVE: To analyze the clinical and genetic characteristics of a patient featuring autosomal dominant Olmsted syndrome. METHODS: Clinical features of the patient was reviewed. High-throughput sequencing was carried out to detect potential genetic variants. RESULTS: The proband, a 12-year-old girl, featured excessive keratinization on hands and feet, contracture of finger joints, and abnormal position and residual contraction of the fifth toes. Skin biopsy showed significant hyperkeratosis, epidermal hyperplasia, and mild interepidermal cell edema. A de novo heterozygous missense variant c.2016G>T(p.Met672Ile) was identified in the TRPV3 gene by high-throughout sequencing. The result was verified by Sanger sequencing. CONCLUSION The destructive palmoplantar keratosis in the child may be attributed to the c.2016G>T(p.Met672Ile) variant of the TRPV3 gene. Aboving finding has provided new evidence for the correlation of genetic variants with clinical phenotypes of Olmsted syndrome.
Child ; Female ; Heterozygote ; Humans ; Keratoderma, Palmoplantar/genetics* ; Skin ; Syndrome ; TRPV Cation Channels/genetics*

Mast cells are activated by specific allergens and also by various nonspecific stimuli, which might induce physical urticaria. This study investigated the functional expression of temperature sensitive transient receptor potential vanilloid (TRPV) subfamily in the human mast cell line (HMC-1) using whole-cell patch clamp techniques. The temperature of perfusate was raised from room temperature (RT, 23~25degrees C to a moderately high temperature (MHT, 37~39degrees C to activate TRPV3/4, a high temperature (HT, 44~46degrees C to activate TRPV1, or a very high temperature (VHT, 53~55degrees C to activate TRPV2. The membrane conductance of HMC-1 was increased by MHT and HT in about 50% (21 of 40) of the tested cells, and the I/V curves showed weak outward rectification. VHT-induced current was 10-fold larger than those induced by MHT and HT. The application of the TRPV4 activator 4alpha-phorbol 12,13-didecanoate (4alphaPDD, 1microM) induced weakly outward rectifying currents similar to those induced by MHT. However, the TRPV3 agonist camphor or TRPV1 agonist capsaicin had no effect. RT-PCR analysis of HMC-1 demonstrated the expression of TRPV4 as well as potent expression of TRPV2. The [Ca2+]c of HMC-1 cells was also increased by MHT or by 4alphaPDD. In summary, our present study indicates that HMC-1 cells express Ca2+-permeable TRPV4 channels in addition to the previously reported expression of TRPV2 with a higher threshold of activating temperature.
Allergens ; Camphor ; Capsaicin ; Humans ; Mast Cells ; Membranes ; Patch-Clamp Techniques ; Phorbols ; TRPV Cation Channels ; Urticaria