Inhibition of acid-sensing ion channels in articular chondrocytes by amiloride attenuates articular cartilage destruction in rats with adjuvant arthritis

Abstract

These findings represent some experimental evidence of a potential role for ASICs in the pathogenesis of articular cartilage destruction in rheumatoid arthritis.

Novel Insights into Acid-Sensing Ion Channels: Implications for Degenerative Diseases

“…Interestingly, matrix turnover is influenced by changes in chondrocytes exposed to extracellular acidosis [71]. Recently, to determine the potential involvement of ASICs in cartilage injury, our group tested the effects of amiloride both in vitro and in vivo [72]. We observed a significant increase in intracellular calcium in articular chondrocytes exposed to extracellular pH 6.0.…”

Blockade of acid-sensing ion channels protects articular chondrocytes from acid-induced apoptotic injury

“…i ) [8]. In addition, our previous studies indicated that inhibiting ASICs by amiloride provides protection for the articular cartilage in adjuvant arthritis rats [12]. Previous studies have indicated that elevation of Ca 2?…”

Acid-sensing ion channels in healthy and degenerated human intervertebral disc

“…Although previous studies in rats demonstrated expression of ASIC3 in both the AF and NP (19,20), as far as we know, the expression of ASICs in human IVD is reported here for the first time. ASICs and other ion channels involved in the control of osmolarity and pH are expressed by chondrocytes in different anatomical localizations and animal species (8,17,18,(26)(27)(28)(29)(30)(31)(32), and therefore it can be assumed that they play identical or similar roles in chondrocytes and chondrocyte-related cells as in other cells. Figure 2. (a) Western blot detection of ASIC proteins in homogenates of healthy human intervertebral disc.…”

“…The pH values required for half-maximal activation are 6.2-6.8 for ASIC1a, 5.9-6.2 for ASIC1b, $4.9 for ASIC2a and 6.5-6.7 for ASIC3 (13). In addition, some ASICs may function as mechanosensors or are required for mechanosensation in a diverse range of species and cell types (9,14,15) and are expressed in a wide range of cells of the muscle skeletal system (16)(17)(18). Recently, Uchiyama et al (19,20) reported the occurrence of ASIC3 in rat IVD cells, and suggested that this ion channel is required for survival of NP cells in acidic and hypertonic medium.…”