Abstract
ObjectiveThe periodontal ligament (PDL) is exposed to constant mechanical forces potentiated by orthodontic tooth movement (OTM). The aim of our study was to investigate the involvement of chaperone-assisted selective autophagy (CASA) in mechanosensing and cellular adaption to forces in the PDL.Materials and methodsHuman PDL cells were loaded with 2.5, 5, and 10% of static mechanical strain for 24 h in vitro. Untreated cells served as controls. Gene expression of HSPA8, HSPB8, BAG3, STUB1, SYNPO2 was investigated via RT-qPCR (Quantitative reverse transcription PCR). Western blot evidenced protein expression of these molecules and of Filamin A. In vivo analyses of CASA were performed via immunohistochemistry on teeth with and without OTM.ResultsCASA machinery genes were inherently expressed in PDL cells and exhibited transcriptional induction upon mechanical strain. Protein analyses underlined these findings, even though modulation upon force exertion also demonstrated a decrease for some molecules and loading strengths. In vivo results evidenced again the uniform upregulation of HSPA8, HSPB8, BAG3, STUB1, SYNPO2 and Filamin A in teeth with OTM compared to controls. Experiments generally evidenced a pronounced variability in the expression between donors both on the gene and protein level.ConclusionsOur study is the first to identify both the expression and functional relevance of CASA in the PDL. The data reflect its probable central role in adequate adaption to forces exerted by OTM and in mechanical stress protection of cells. Deeper knowledge of the CASA pathway will allow better assessment of predisposing factors regarding side effects during mechanical force application that can be used in orthodontic practice.
Highlights
The periodontal ligament (PDL) represents a mechanically challenged tissue due to its location at the interface between teeth and bone, that has to cope with mechanical forces to maintain cellular viability and homeostasis [2, 10, 16]
chaperone-assisted selective autophagy (CASA) complex component expression was markedly upregulated when mechanical loading was exerted on PDL cells, which applied for all strain intensities applied
After analyzing BAG3, STUB1, HSPA8, HSPB8, and SYNPO2 at the genetic level, we looked at the protein expression of these molecules and investigated whether the pattern is congruent to the transcriptional profile
Summary
The periodontal ligament (PDL) represents a mechanically challenged tissue due to its location at the interface between teeth and bone, that has to cope with mechanical forces to maintain cellular viability and homeostasis [2, 10, 16]. Failure to adequately adapt to mechanical load or overload may initiate the pathobiological mechanisms for cellular membrane damage, cell death and subsequent tissue destruction [22]. Root resorption as a harmful side effect of OTM might occur if the cellular processes cannot be modulated properly [5]. Investigations on other tissues identified a major impact of the processes of protein synthesis and degradation, which seem to be able to orchestrate adaption to mechanical forces, as being important [8, 13, 20, 22]. A fine-tuned balance is considered prerequisite for protein homeostasis of cells, so-called proteostasis [13]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callMore From: Journal of Orofacial Orthopedics / Fortschritte der Kieferorthopädie
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
