Platelet-Derived Growth Factor Receptor-α and β are Involved in Fluid Shear Stress Regulated Cell Migration in Human Periodontal Ligament Cells
Fluid shear stress (FSS) is the most common stress produced by mastication, speech, or tooth movement. However, how FSS regulates human periodontal ligament (PDL) cell proliferation and migration as well as the underlying mechanism remains unknown.
FSS (6 dyn/cm2) was produced in a flow chamber. Cell proliferation was tested by the 5-ethynyl-2′-deoxyuridine assay. Cell migration was tested by the wound healing assay. Gene and protein expression of platelet-derived growth factors (PDGFs) and matrix metalloproteinase (MMP)-2 were measured by reverse transcription-polymerase chain reaction and western blot analyses.
We investigated the effect of 4 h of 6 dyn/cm2 FSS on proliferation and migration of PDL cells. FSS promoted PDL cell proliferation but inhibited migration. The gene and protein expression of PDGF receptor (PDGFR)-α and β both decreased in response to FSS. Activating and inhibiting the PDGFRs did not affect the FSS-induced increase in cell proliferation. However, activating PDGFRs with PDGF-BB, which bound both PDGFR-α and β, and PDGF-CC and DD, which had high affinities for PDGFR-α and PDGFR-β, individually rescued FSS-inhibited migration. FSS also inhibited MMP-2 gene expression, which was the most important factor for matrix turnover and migration of PDLs. PDGF-BB, CC, and DD increased the FSS-induced decline in MMP-2 expression. These results indicate that MMP-2 is regulated by FSS and contributes to the FSS-induced decrease in cell migration.
Our study suggests a role for PDGFR-α and β in short-term FSS-regulated cell proliferation and migration. These results will help provide the scientific foundation for revealing the mechanisms clinical tooth movement and PDL regeneration.
KeywordsPDGF receptor Proliferation Migration Matrix metalloproteinases-2
Platelet-derived growth factors
Fluid shear stress
Mitogen-activated protein kinase
Dulbecco’s modified Eagle medium
Fetal bovine serum
Phenylmethane sulfonyl fluoride
Sodium dodecyl sulfate polyacrylamide gel electrophoresis
Triethanolamine buffered saline solution
Mesenchymal stem cell
Smooth muscle cell
This work was supported by National Natural Science Foundation of China (Grant Numbers 11572030), National Key R&D Program of China (2017YFC0108505); National Natural Science Foundation of China (Grant Numbers 11120101001, 11421202); the Fundamental Research Funds for the Central Universities; the 111 Project (Grant Numbers B13003).
Conflict of interest
All authors including Lisha Zheng, Qiusheng Shi, Jing Na, Nan Liu, Yuwei Guo, Yubo Fan have no conflicts of interest.
The authors state that all human subjects research was carried out in accordance with the Declaration of Helsinki and approved by Beihang University Ethics Committee. This study did not involve any animal research.
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