Background:

osteocytes are capable of detecting different signals, transducing them into biological responses and transmitting them to osteoblasts and osteoclasts, allowing the maintenance of bone homeostasis. Bone mechanotransduction is possible because osteocytes have different mechanosensor structures such as connexins (Cxs), integrins, the primary cilium and even receptors coupled to G proteins such as the type 1 parathyroid hormone receptor (PTH1R).

Objective:

to analyze the possible interaction of the different mechanosensor elements of the osteocytes and to observe their influence on the biological response.

Material and methods:

we worked with the osteocytic cell lines MLO-Y4 Cx43+/+ (scrambled [SCR] and RNAi α2) and Cx43-/-.

Results and conclusion:

our results show that Cx43 and integrin α2 are involved in lengthening the primary cilium, potentially affecting its functionality as a mechanosensor (SCR vs RNAi α2, p < 0.0001 SCR vs Cx43-/- and p < 0.0001 RNAi α2 vs Cx43-/-). The α2 integrin also influenced the cellular localization of Cx43, promoting its presence in the plasma membrane. Activation of PTH1R by agonists such as parathyroid hormone (PTH) and parathyroid hormone-related protein (PTHrP) was also found to induce ERK 1/2 kinase phosphorylation, and these effects could be affected by Cx43 deficiency, but do not appear to be. mediated by the silencing of α2 integrin. Finally, it was observed that the presence of Cx43 and integrin α2 in osteocytes increases their adhesion capacity (Cx43+/+ SCR and RNAi α2 vs CX43-/- p < 0.001 and p = 0.0039) and that deficiency in Cx43 causes an increase in the mortality of these cells (Cx43-/- vs Cx43+/+ p = 0.0074).

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