Table 3.
The role of ion channels in osteoarthritis
| Study | Cell/Tissue | Ion channel and intenvention | Results |
|---|---|---|---|
| Funabashi et al. (2010) | OUMS-27 cell line | SK channels, CRAC channels, histamine | K+ efflux through SK channels, increased intracellular Ca2+ concentration via nonselective cation channels including CRAC channels, membrane hyperpolarization |
| Li et al. (2017) | Human chondrocytes from OA patients | Piezo1, GsMTx4, a PIEZO-blocking peptide | Suppressed expression of apoptosis-related genes |
| Sooampon et al. (2013) | Human periodontal ligament (HPDL) cells, human osteoblasts | Piezo1, GsMTx4 | Ca2+ influx, attenuated deteriorated response of chondrocytes to injurious mechanical strain |
| O’Conor et al. (2016) | Conditional knockout (cKO) mice | Gene knock down of TRPV4 channel | Decreased total periarticular bone volume, reduced severity of aging-associated OA |
| Ogawa et al. (2019) | The ATDC5 cell line | TRPV4, GSK1016790A, a selective TRPV4 agonist | Activation of TRPV4-ICAM-1-up-regulation of chondrogenic marker genes including SOX9 and ACAN, HA facilitated TRPV4-induced chondrogenesis |
| Srinivasan et al. (2015) | KO and WT mice | Gene knock down of T-type VGCCs | Enhanced cartilage degeneration and subchondral bone resorption |
| Kuduk, S. D., et al. (2010), Izumi, M., et al. (2012) | KO and WT mice, rat osteoarthritis models | Gene knock down of ASIC-3, the ASIC3 inhibitor A-317,567, ASIC3 selective peptide blocker (APETx2) | Altered expression of ASIC3 in knee joint afferents, reversed osteoarthritis pain and mechanical hyperalgesia |
| Schuelert, N., et al. (2010) | Rat osteoarthritis models | The cannabinoid CB2 receptor agonist GW405833 | Reduced mechanosensitivity of afferent nerve fibers in control joints, nociceptive responses in OA joints |
| Shimazaki, A., et al. (2006) | Human normal and OA articular chondrocytes | NMDA receptor(ligand-gated ion channels), CaMKII inhibitor | Inhibited membrane potential, upregulation of aggrecan mRNA |
| Clark et al. (2010) | KO mice | Gene knock down of TRPV4 | Severe OA degeneration |
| Lee et al. (2014) | Murine chondrocytes | Piezo1, GsMTx4, siRNA | Attenuated maladaptive chondrocyte responses |
| Zelenski et al. (2015) | Murine articular chondrocytes | Gene knock down of TRPV4 | Suppressed mechanically induced Ca2+ influx and formation of pericellular matrix |
| Moilanen, L. J., et al. (2015) | Murine articular chondrocytes | Pharmacological blockade and gene knock down of TRPA1 | Suppressed iodoacetate-induced OA |
| O’Conor, C. J., et al. (2016) | cKO mice | Gene knock down of TRPV4 | Reduced severity of aging-associated OA |
| He, B. H., et al. (2017) | OA mice | Mechanosensitive ion channels, the selective inhibitor GsMTx4 | Reduced activation of dorsal horn nociceptive circuits and primary mechanical allodynia |
| Xing, R., et al. (2017) | OA mice | TRPA1, TRPV4 | Upregulation of TRPA1 and TRPV4 mechanical hyperalgesia induced by OA |
| Parisi, C., et al. (2018) | Chick joint | Pharmacological blockade of SACs, VGCCs, | Removed effects of mechanical stimulation on joint cartilage growth and shape development |
| Raouf, R., et al. (2018) | Rat DRG nerons | Piezo2, overexpression and gene knock down of annexin A6 | Attenuated mechanical hyperalgesis induced by OA |
| Richter, F., et al. (2019) | Rat DRG nerons | TRPV4, agonist 4αPDD, GSK 1016790 A and antagonist RN-1734 | Altered mechanonociception of the normal and inflamed joint |
| Xu, B., et al. (2019) | Rat articular chondrocytes | Pharmacological blockade and gene knock down of TRPV4 | Attenuated cartilage degeneration in rat OA anterior cruciate-ligament transection (ALCT) models |
| Nummenmaa, E., et al. (2020) | Rat articular chondrocytes, human OA chondrocytes | Pharmacological blockade and gene knock down of TRPA1 | Downregulation of the pro-inflammatory cytokine interleukin-6 (IL-6), IL-6 family cytokines leukemia inhibitory factor (LIF) and IL-11 |
| Fu, S., et al. (2021) | Rat articular chondrocytes | Pharmacological blockade or activation of TRPV4 | Pro-inflammatory signaling and cartilage degradation |