Pyroptosis, an inflammatory caspase-dependent programmed cell death, plays a vital role in maintaining tissue homeostasis and activating inflammatory responses. Orthodontic tooth movement (OTM) is an aseptic force-induced inflammatory bone remodeling process mediated by the activation of periodontal ligament (PDL) progenitor cells. However, whether and how force induces PDL progenitor cell pyroptosis, thereby influencing OTM and alveolar bone remodeling remains unknown. In this study, we found that mechanical force induced the expression of pyroptosis-related markers in rat OTM and alveolar bone remodeling process. Blocking or enhancing pyroptosis level could suppress or promote OTM and alveolar bone remodeling respectively. Using Caspase-1^-/- mice, we further demonstrated that the functional role of the force-induced pyroptosis in PDL progenitor cells depended on Caspase-1. Moreover, mechanical force could also induce pyroptosis in human ex-vivo force-treated PDL progenitor cells and in compressive force-loaded PDL progenitor cells in vitro, which influenced osteoclastogenesis. Mechanistically, transient receptor potential subfamily V member 4 signaling was involved in force-induced Caspase-1-dependent pyroptosis in PDL progenitor cells. Overall, this study suggested a novel mechanism contributing to the modulation of osteoclastogenesis and alveolar bone remodeling under mechanical stimuli, indicating a promising approach to accelerate OTM by targeting Caspase-1.
Animals ; Humans ; Mice ; Rats ; Bone Remodeling/physiology* ; Caspase 1 ; Periodontal Ligament ; Pyroptosis ; Tooth Movement Techniques

The bone remodeling process in response to orthodontic forces requires the activity of osteoclasts to allow teeth to move in the direction of the force applied. Receptor activator of nuclear factor-κB ligand (RANKL) is essential for this process although its cellular source in response to orthodontic forces has not been determined. Orthodontic tooth movement is considered to be an aseptic inflammatory process that is stimulated by leukocytes including T and B lymphocytes which are presumed to stimulate bone resorption. We determined whether periodontal ligament and bone lining cells were an essential source of RANKL by tamoxifen induced deletion of RANKL in which Cre recombinase was driven by a 3.2 kb reporter element of the Col1α1 gene in experimental mice (Col1α1.CreER.RANKL) and compared results with littermate controls (Col1α1.CreER.RANKL). By examination of Col1α1.CreER.ROSA26 reporter mice we showed tissue specificity of tamoxifen induced Cre recombinase predominantly in the periodontal ligament and bone lining cells. Surprisingly we found that most of the orthodontic tooth movement and formation of osteoclasts was blocked in the experimental mice, which also had a reduced periodontal ligament space. Thus, we demonstrate for the first time that RANKL produced by periodontal ligament and bone lining cells provide the major driving force for tooth movement and osteoclastogenesis in response to orthodontic forces.
Animals ; Bone Remodeling ; physiology ; Mice ; Mice, Transgenic ; Osteoclasts ; physiology ; Periodontal Ligament ; metabolism ; RANK Ligand ; metabolism ; Tamoxifen ; pharmacology ; Tooth Movement Techniques

Bone remodeling is balanced by bone formation and bone resorption as well as by alterations in the quantities and functions of seed cells, leading to either the maintenance or deterioration of bone status. The existing evidence indicates that microRNAs (miRNAs), known as a family of short non-coding RNAs, are the key post-transcriptional repressors of gene expression, and growing numbers of novel miRNAs have been verified to play vital roles in the regulation of osteogenesis, osteoclastogenesis, and adipogenesis, revealing how they interact with signaling molecules to control these processes. This review summarizes the current knowledge of the roles of miRNAs in regulating bone remodeling as well as novel applications for miRNAs in biomaterials for therapeutic purposes.
Animals ; Bone Remodeling ; physiology ; Cell Lineage ; Humans ; MicroRNAs ; physiology ; Osteoblasts ; cytology ; Transcription, Genetic

Animals ; Biomechanical Phenomena ; Bone Development ; Bone Remodeling ; Bone and Bones ; injuries ; Fracture Healing ; physiology ; Fractures, Bone ; pathology

OBJECTIVETo investigate the correlation of serum sex hormones and parathyroid hormone (PTH) with the biochemical markers of bone turnover in aged men.

METHODSWe collected the laboratory data of 465 men aged 60- 93 (73. 1 +/- 8. 3) years old, who came for routine physical examinations in our hospital. We obtained the levels of serum follicle- stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), testosterone (T), sex hormone binding globulin (SHBG), PTH, 25-hydroxy-vitamin D3 (25(OH) D3), and bone turnover markers C-terminal telopeptide of type I collagen (CTX), osteocalcin (OC) and amino-terminal propeptide of type I procollagen (PINP). We also determined free testosterone (FT) , bioactive testosterone (BT) , testosterone secretion index (TSI) and FT index (FTI), and analyzed the correlation of each index with the biochemical markers of bone turnover.

RESULTSThe concentrations of serum FSH, LH, and SHBG increased, while the levels of FT, BT, TSI, FTI, PTH, CTX, OC and PINP decreased with age, especially in those over 80 years old (P <0.05). PTH was positively correlated with CTX, OC and PINP (r =0. 227, 0. 269 and 0. 162, P <0. 01), even after the adjustment for age, while SHBG negatively correlated with OC (r = -0. 100, P <0.05). The bone turnover markers increased with the elevation of the PTH quartiles, with significant differences between the first and the fourth quartile (P <0. 01). Multiple stepwise regression analysis showed that age was correlated inversely with CTX, OC and PINP ( beta = -0. 126, -0. 141 and -0. 122, P <0.05) , PTH positively with the three markers (beta = 0. 196, 0.279 and 0.189; P <0. 001), and SHBG negatively with OC ( beta = -0. 100, P <0.05) .

CONCLUSIONAging is the fundamental cause of reduced bone turnover in aged men. The levels serum PTH and SHBG are significantly associated with the biochemical markers of bone turnover.

Aged ; Aged, 80 and over ; Aging ; Bone Density ; Bone Remodeling ; physiology ; Bone and Bones ; metabolism ; Estradiol ; blood ; Follicle Stimulating Hormone ; blood ; Gonadal Steroid Hormones ; blood ; Humans ; Male ; Middle Aged ; Parathyroid Hormone ; blood ; Testosterone ; blood

Bidirectional Eph-Ephrin signaling as a focal point of research in cell-cell communications is critical for generation of nerves and vesssels as well as invation and metastasis of tumor cells. The roles for Ephrin-Eph bidirectional signaling in bone remodeling were important. EphrinB2 is expressed on osteoblasts and EphB4 is expressed on osteoclasts. Forward signaling through the EphB4 receptor into mesenchymal precursors promotes osteoblast differentiation, while reverse signaling through the EphrinB2 ligand into osteoclast suppresses differentiation. Signaling between the ligand EphrinB2 and the receptors EphB4 explains bidirectional signaling between osteoblasts and osteoclasts,bone absorption and remodeling, which may lay a theoretical foundation for identifying drug targeting and preventing and treating bone loss.
Animals ; Bone Remodeling ; physiology ; Ephrin-B2 ; physiology ; Humans ; Osteoblasts ; cytology ; Osteoclasts ; cytology ; Receptor, EphB4 ; physiology ; Signal Transduction ; physiology

OBJECTIVETo study the remodeling of the anterior alveolar bone with parodontium under physiology loading using finite element method (FEM) and theory of bone remodeling.

METHODSA FEM model of the maxillary central incisor with parodontium was established, and the change of bone density during the remodeling of alveolar bone was investigated under physiology loading (60 - 150 N) based on the theory of bone remodeling about strain energy density (SED). The finite element analysis software Abaqus user material subroutine (UMAT) were used.

RESULTSWith the increase of physiology loading, the pressure stress on the buccal cervical margin increased gradually while the density was decreased gradually. The cortical bone was lower than its initial density 1.74 g/cm(3), which was 1.74 - 1.63 g/cm(3). The density of cancellous bone was 0.90 - 0.77 g/cm(3), which was lower than its intial density 0.90 g/cm(3). The lingual cervical margin was under tensile stress which also increased with loading, the density had no significant change. When the achieve to 120 N, the density of cortical bone was 1.74 - 1.73 g/cm(3). No significant change was found in the cancellous bone.

CONCLUSIONSThe simulation of the perodontium remodeling is achieved and proved to be effective by the relevant research based on the method of the study. And the result will be helpful to form the basis of analysis bone remodeling process and predict the results in the clinical work.

Alveolar Process ; physiology ; Bone Density ; Bone Remodeling ; physiology ; Computer Simulation ; Dental Stress Analysis ; methods ; Finite Element Analysis ; Humans ; Incisor ; physiology ; Maxilla ; physiology ; Periodontium ; physiology ; Stress, Mechanical

Osteogenesis and angiogenesis are two closely correlated processes during bone growth, development, remodelling and repair.Vascular endothelial growth factor (VEGF) is an essential mediator during the process of angiogenesis. Based on an extensive literature search, which was carried out using the PubMed database and the keywords of osteogenesis, VEGF, endochondral ossification and intramembranous ossification, this manuscript reviews the role of VEGF in ossification, with emphasis on its effect in endochondral and intramembranous ossification. Osteogenesis and angiogenesis are closely correlated processes. VEGF acts as an essential mediator during these processes. It not only functions in bone angiogenesis but also in various aspects of bone development.
Animals ; Bone Remodeling ; physiology ; Bone and Bones ; cytology ; physiology ; Calcification, Physiologic ; physiology ; Cartilage ; cytology ; physiology ; Humans ; Neovascularization, Physiologic ; physiology ; Osteoclasts ; physiology ; Osteogenesis ; physiology ; Vascular Endothelial Growth Factor A ; physiology

Dental implant is an advanced prosthodontic treatment widely accepted by patients with missing tooth. However, peri-implant bone loss is still an important reason which limits wider application of the implants to a certain extent. Bisphosphonates is an osteoclastic bone resorption inhibitor that is widely used in clinical practice with the function of inhibiting bone resorption and increasing bone density. As the defect of systemic BPs treatment, local application of BPs in implant has become a research hotspot recently. Calcium phosphate ceramics, polylactic acid, fibrinogen film and collagen membrane have been reported as BPs carriers. This article summarizes the researches on the mechanism of bone regulation and local delivering system of BPs.
Administration, Topical ; Bone Density Conservation Agents ; administration & dosage ; Bone Remodeling ; drug effects ; physiology ; Dental Implantation, Endosseous ; methods ; Dental Implants ; Diphosphonates ; administration & dosage ; Humans

Peroxisome proliferator activated receptor gamma interacts with bone morphogenetic protein, Wnt, TAZ, and insulin-like growth factor-I, which are required for the process of osteoblast differentiation, regulating the mesenchymal stem cells (MSCs) into adipocytes and osteoblasts differentiation, thus impact on the osteoblast-mediated bone formation in bone remodeling, and, through RANKL and other factors directly or indirectly, regulate osteoclast-mediated bone resorption. This article reviews new researches for the influence of peroxisome proliferator activated receptor gamma on osteoblast and osteoclast function in bone remodeling.
Bone Remodeling ; physiology ; Humans ; Osteoblasts ; physiology ; Osteoclasts ; physiology ; PPAR gamma ; physiology