Abstract
Mature and developing chondrocytes exist in a microenvironment where mechanical load, changes of temperature, osmolarity and acidic pH may influence cellular metabolism. Polymodal Transient Receptor Potential Vanilloid (TRPV) receptors are environmental sensors mediating responses through activation of linked intracellular signalling pathways. In chondrogenic high density cultures established from limb buds of chicken and mouse embryos, we identified TRPV1, TRPV2, TRPV3, TRPV4 and TRPV6 mRNA expression with RT-PCR. In both cultures, a switch in the expression pattern of TRPVs was observed during cartilage formation. The inhibition of TRPVs with the non-selective calcium channel blocker ruthenium red diminished chondrogenesis and caused significant inhibition of proliferation. Incubating cell cultures at 41 °C elevated the expression of TRPV1, and increased cartilage matrix production. When chondrogenic cells were exposed to mechanical load at the time of their differentiation into matrix producing chondrocytes, we detected increased mRNA levels of TRPV3. Our results demonstrate that developing chondrocytes express a full palette of TRPV channels and the switch in the expression pattern suggests differentiation stage-dependent roles of TRPVs during cartilage formation. As TRPV1 and TRPV3 expression was altered by thermal and mechanical stimuli, respectively, these are candidate channels that contribute to the transduction of environmental stimuli in chondrogenic cells.
Highlights
Articular cartilage is a unique tissue with a low density of chondrocytes, where this sole cell type is capable of secreting and maintaining the abundant cartilaginous extracellular matrix (ECM)
Since certain Transient Receptor Potential Vanilloid (TRPV) are suggested contributing to mechanosensation in various cell types [32], we aimed to find out whether cyclic uniaxial mechanical load influenced the mRNA expression level of TRPV receptors
There are no articles describing if TRPV3 is linked to mechanotransduction of cells, we find it interesting that the mRNA of TRPV3 increased significantly, compared to the rest of the ion channels
Summary
Articular cartilage is a unique tissue with a low density of chondrocytes, where this sole cell type is capable of secreting and maintaining the abundant cartilaginous extracellular matrix (ECM). Since one of the key roles of articular cartilage is to distribute mechanical load and absorb shock generated during physical activity between opposing bones, chondrocytes are inherently adapted to the demands imposed by mechanical stimuli. Despite their low metabolic activity, chondrocytes communicate extensively with their environment partly through the dynamically changing ECM and respond to a range of mechanical and biochemical stimuli. Oxygen tension is gradually decreasing to as low as
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