Intermittent compressive force regulates human periodontal ligament cell behavior via yes-associated protein

Nuttha Klincumhom; Chanchao Lorthongpanich; Kanjana Thumanu; Praphasri Septham; Wutthikiat Phomyu; Surapol Issaragrisil; Prasit Pavasant

doi:10.1016/j.heliyon.2022.e10845

Intermittent compressive force regulates human periodontal ligament cell behavior via yes-associated protein

Heliyon. 2022 Oct 1;8(10):e10845. doi: 10.1016/j.heliyon.2022.e10845. eCollection 2022 Oct.

Authors

Nuttha Klincumhom¹, Chanchao Lorthongpanich², Kanjana Thumanu³, Praphasri Septham², Wutthikiat Phomyu¹, Surapol Issaragrisil², Prasit Pavasant¹

Affiliations

¹ Center of Excellence for Regenerative Dentistry and Department of Anatomy, Faculty of Dentistry, Chulalongkorn University, Bangkok 10330, Thailand.
² Siriraj Center of Excellence for Stem Cell Research, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand.
³ Synchrotron Light Research Institute (Public Organization), Nakhon Ratchasima, Thailand.

Abstract

Intermittent compressive force influences human periodontal ligament (PDL) cell behavior that facilitates periodontal tissue regeneration. In response to mechanical stimuli, Yes-associated protein (YAP) has been recognized as a mechanosensitive transcriptional activator that regulates cell proliferation and cell fate decisions. This study aimed to investigate whether compressive forces influence cell proliferation and cell fate decisions of human PDL cells via YAP signaling. YAP expression was silenced by shRNA. The effect of YAP on cell proliferation, adipogenesis and osteogenesis of PDL cells under ICF loading were determined. Adipogenic differentiation bias upon ICF loading was confirmed by fourier-transform infrared spectroscopy (FTIR). The results revealed that ICF-induced YAP promotes osteogenesis, but it inhibits adipogenesis in PDL cells. Depletion of YAP results in PDL cells that are irresponsive to ICF and, therefore, the failure of the PDL cells to undergo osteogenic differentiation. This was shown by a significant reduction in calcium deposited in the CF-derived osteoblasts of the YAP-knockdown (YAP-KD) PDL cells. As to control treatment, reduction of YAP promoted adipogenesis, whereas ICF-induced YAP inhibited this mechanism. However, the adipocyte differentiation in YAP-KD cells was not affected upon ICF treatment as the YAP-KD cells still exhibited a better adipogenic differentiation that was unrelated to the ICF. This study demonstrated that, in response to ICF treatment, YAP could be a crucial mechanosensitive transcriptional activator for the regulation of PDL cell behavior through a mechanobiological process. Our results may provide the possibility of facilitating PDL tissue regeneration by manipulation of the Hippo-YAP signaling pathway.

Keywords: Cell fate decision; FTIR; Hippo signaling pathway; Human periodontal ligament cells; Intermittent compressive force; Yes-associated protein.