Abstract
Autophagy is a lysosomal protein degradation system in which the cell self-digests its intracellular protein components and organelles. Defects in autophagy contribute to the pathogenesis of age-related chronic diseases, such as myocardial infarction and rheumatoid arthritis, through defects in the extracellular matrix (ECM). However, little is known about autophagy in periodontal diseases characterised by the breakdown of periodontal tissue. Tooth-supportive periodontal ligament (PDL) tissue contains PDL cells that produce various ECM proteins such as collagen to maintain homeostasis in periodontal tissue. In this study, we aimed to clarify the physiological role of autophagy in periodontal tissue. We found that autophagy regulated type I collagen synthesis by elimination of misfolded proteins in human PDL (HPDL) cells. Inhibition of autophagy by E-64d and pepstatin A (PSA) or siATG5 treatment suppressed collagen production in HPDL cells at mRNA and protein levels. Immunoelectron microscopy revealed collagen fragments in autolysosomes. Accumulation of misfolded collagen in HPDL cells was confirmed by sodium dodecyl sulfate–polyacrylamide gel electrophoresis. E-64d and PSA treatment suppressed and rapamycin treatment accelerated the hard tissue-forming ability of HPDL cells. Our findings suggest that autophagy is a crucial regulatory process that facilitates type I collagen synthesis and partly regulates osteoblastic differentiation of PDL cells.
Highlights
Periodontal ligament (PDL) tissue is a connective tissue consisting of rich collagenous fibres with elastic properties, which is located between the cementum and alveolar bone
Transmission electron microscopy (TEM) analysis revealed the induction of microvacuole formation in human PDL (HPDL) cells after 4 h of serum starvation in culture with Hank’s balanced saline solution (HBSS) (Fig. 1A)
We investigated the role of autophagy in homeostasis of periodontal ligament (PDL) tissues by using primary HPDL cells in vitro
Summary
Periodontal ligament (PDL) tissue is a connective tissue consisting of rich collagenous fibres with elastic properties, which is located between the cementum and alveolar bone. Comprehensive gene analysis of PDL from extracted human teeth has revealed constitutive expression of type I and III collagens, as well as ribosomal function-related genes involved in protein translation in PDL c ells[9]. These findings strongly indicate that ECM proteins are actively synthesised in PDL, as well as in chondrocytes and tendon tissue. Macroautophagy (hereafter referred to as autophagy) is the lysosomal protein degradation system in which the cell self-digests its protein components and organelles to maintain cellular homeostasis. Autophagy machinery might be important for wound healing and tissue regeneration by accelerating the hard tissue-forming ability of PDL cells through collagen synthesis
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