Compressive force‐induced LincRNA‐p21 inhibits mineralization of cementoblasts by impeding autophagy

Abstract

The mineralization capability of cementoblasts is the foundation for repairing orthodontic treatment‐induced root resorption. It is essential to investigate the regulatory mechanism of mineralization in cementoblasts under mechanical compression to improve orthodontic therapy. Autophagy has a protective role in maintaining cell homeostasis under environmental stress and was reported to be involved in the mineralization process. Long noncoding RNAs are important regulators of biological processes, but their functions in compressed cementoblasts during orthodontic tooth movement remain unclear. In this study, we showed that compressive force downregulated the expression of mineralization‐related markers. LincRNA‐p21 was strongly enhanced by compressive force. Overexpression of lincRNA‐p21 downregulated the expression of mineralization‐related markers, while knockdown of lincRNA‐p21 reversed the compressive force‐induced decrease in mineralization. Furthermore, we found that autophagy was impeded in compressed cementoblasts. Then, overexpression of lincRNA‐p21 decreased autophagic activity, while knockdown of lincRNA‐p21 reversed the autophagic process decreased by mechanical compression. However, the autophagy inhibitor 3‐methyladenine abolished the lincRNA‐p21 knockdown‐promoted mineralization, and the autophagy activator rapamycin rescued the mineralization inhibited by lincRNA‐p21 overexpression. Mechanistically, the direct binding between lincRNA‐p21 and FoxO3 blocked the expression of autophagy‐related genes. In a mouse orthodontic tooth movement model, knockdown of lincRNA‐p21 rescued the impeded autophagic process in cementoblasts, enhanced cementogenesis, and alleviated orthodontic force‐induced root resorption. Overall, compressive force‐induced lincRNA‐p21 inhibits the mineralization capability of cementoblasts by impeding the autophagic process.

Autophagy mediates cementoblast mineralization through periostin/β-catenin signaling axis under compression

“…In particular, the effects of compressive force on cementoblast mineralization are ambiguous. Our previous study found that orthodontic force inhibits cementoblast mineralization in vivo 27 . Consistent with previous ndings, the present study also showed an adverse effect of compressive stimulation on cementoblast mineralization.…”

“…Application of orthodontic mechanical force was performed as described previously 27 . A nickel-titanium coil spring (wire size, 0.2 mm; Smart Technology, Beijing, China) was used to connect the right maxillary rst molar and maxillary incisors and provided a nearly constant force of approximately 20 g. Mice were randomly divided into different groups according to the duration of force applied (0, 1, 2, or 3 weeks), with ve mice in each group.…”

Alterations between Autophagy and Apoptosis in Alveolar Bone Mesenchymal Stem Cells under Orthodontic Force and Their Effects on Osteogenesis

“…Hypoxia also induces apoptosis in cementoblasts by restricting the SIRT1-induced autophagy pathway 33) . In addition, cementoblasts and periodontal ligament stem cells (PDLSCs) have also been shown to be regulated by autophagy through signaling pathways mediated by non-coding RNAs under stress 1,34) . However, during orthodontic tooth movement, the relationship between the autophagy and apoptosis of BMSCs has yet to be fully elucidated; moreover, we know little of the molecular mechanisms involved in osteogenic differentiation.…”

“…Autophagy and apoptosis are both important cytological processes that occur during orthodontic tooth movement and regulate alveolar bone resorption on the pressure side [1][2][3][4] . Studies have shown that osteocyte apoptosis on an orthodontic pressure side is one of the most important mechanisms that lead to bone resorption 4) .…”

Macrophages with Different Polarization Phenotypes Influence Cementoblast Mineralization through Exosomes

“…In vivo experiments were performed using 6week-old male C57BL/6 mice. The mechanical forceinduced OTM model was performed using a previously described protocol [23]. After general anesthesia, a nickeltitanium coil spring was placed between the right maxillary first molar and maxillary incisors to provide an almost constant force of approximately 30g.…”