PDGF-AA promotes gap junction intercellular communication in chondrocytes via the PI3K/Akt pathway

ABSTRACT

Background

Gap junction intercellular communication (GJIC) plays an important role in cell growth, development and homeostasis. Connexin 43 (Cx43) is an important half-channel protein responsible for gap junction formation. Platelet-derived growth factor AA (PDGF-AA) regulates the proliferation, migration, metabolism, apoptosis and cell cycle of chondrocytes. However, the role of PDGF-AA in gap junction intercellular communication in chondrocytes is not fully understood. In the current study, we performed experiments to explore the effect of PDGF-AA on GJIC and its underlying biomechanical mechanism.

Methods

qPCR was performed to determine the expression of PDGF, PDGFR and connexin family genes in chondrocytes and/or cartilage. A scrape loading/dye transfer assay was used to determine GJIC. Western blot analysis was applied to detect the expression of Cx43 and PI3K/Akt signaling pathway proteins. Immunofluorescence staining was utilized to examine protein distribution. Scanning electron microscopy was used to delineate the morphology of chondrocytes.

Results

Expression of PDGF-A mRNA was highest among the PDGF family in chondrocytes and cartilage tissues. PDGF-AA promoted functional GJIC formation in chondrocytes by upregulating the expression of Cx43. Enhanced functional GJIC formation in chondrocytes induced by PDGF-AA occurred through the activation of PI3K/Akt signaling and its nuclear accumulation.

Conclusion

For the first time, this study provides evidence demonstrating the role of PDGF-AA in cell-to-cell communication in chondrocytes through mediating Cx43 expression.

KEYWORDS:

• Platelet-derived growth factor AA
• chondrocytes
• gap junction intercellular communication
• Phosphatidylinositol 3-kinase/protein kinase B signaling pathway

Acknowledgments

We acknowledged Dr. Yunfei Tian in the Analytical and Testing Centre of Sichuan University for his excellent assistance in AFM imaging.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Supplementary material

Supplemental data for this article can be accessed here.

Data availability statement

Any raw data involving this study are available from the corresponding authors on request.

Additional information

Funding

National Natural Science Foundation of China [81371136,81430011,81670978,81771047,81870754];