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

Bone formation and deposition are initiated by sensory nerve infiltration in adaptive bone remodeling. Here, we focused on the role of Semaphorin 3A (Sema3A), expressed by sensory nerves, in mechanical loads-induced bone formation and nerve withdrawal using orthodontic tooth movement (OTM) model. Firstly, bone formation was activated after the 3rd day of OTM, coinciding with a decrease in sensory nerves and an increase in pain threshold. Sema3A, rather than nerve growth factor (NGF), highly expressed in both trigeminal ganglion and the axons of periodontal ligament following the 3rd day of OTM. Moreover, in vitro mechanical loads upregulated Sema3A in neurons instead of in human periodontal ligament cells (hPDLCs) within 24 hours. Furthermore, exogenous Sema3A restored the suppressed alveolar bone formation and the osteogenic differentiation of hPDLCs induced by mechanical overload. Mechanistically, Sema3A prevented overstretching of F-actin induced by mechanical overload through ROCK2 pathway, maintaining mitochondrial dynamics as mitochondrial fusion. Therefore, Sema3A exhibits dual therapeutic effects in mechanical loads-induced bone formation, both as a pain-sensitive analgesic and a positive regulator for bone formation.
Humans ; Bone Remodeling ; Cell Differentiation ; Osteogenesis ; Semaphorin-3A/pharmacology* ; Trigeminal Ganglion/metabolism*

OBJECTIVE: To evaluate the effect of denosumab on bone mineral density around proximal femoral prosthesis after total hip arthroplasty(THA) in the postmenopausal osteoporotic patients. METHODS: Fifty-four consecutive patients underwent unilateral primary THA were included in this retrospective study. Twenty-five patients received denosumab for osteoporosis as the treatment group, and the twenty-nine without denosumab were the control group. At 1 week, 3month, 6 months, and 12 months after THA, bone turnover markers and proximal femoral periprosthetic bone mineral density (BMD) were measured. RESULTS: At 3, 6 and 12 months after operation, the level of TRACP-5b in the control group was significantly higher than that in the treatment group (P<0.05);the level of bone-specific alkaline phosphatase (BALP) between two groups showed significant difference in 12 months after operation (control group was higher than treatment group, P<0.05). The BMD of Gruen 1 and Gruen 7 decreased at 3, 6 and 12 months after operation compared with 1 week after operation. Comparing the treatment group and the control group, the differences of the the decrease of BMD in Gruen 1 and Gruen 7 were no significant at 3 months after surgery. In Gruen 1, Gruen 7 at 6 months after operation and Gruen 1, Gruen 7 at 12 months after operation, the decrease of BMD in the control group was significantly higher than that in the treatment group(P<0.05). It is suggested that desudumab could inhibit the loss of BMD after 6 months, and continuously show a protective effect on bone mass at 12 months after operation. CONCLUSION After THA in postmenopausal patients with osteoporotic femoral neck fracture, Desuzumab can reduce the loss of BMD around the proximal femoral prosthesis and effectively inhibit bone resorption.
Humans ; Arthroplasty, Replacement, Hip ; Bone Density ; Denosumab/therapeutic use* ; Retrospective Studies ; Postmenopause ; Absorptiometry, Photon ; Bone Remodeling ; Follow-Up Studies ; Hip Prosthesis

OBJECTIVE: To determine whether resveratrol (Res) can correct osteoporosis induced in a rat model of male hypogonadism. METHODS: Thirty-two rats were randomly divided into 4 groups, 8 in each group; 1) a control sham group: underwent a similar surgical procedure for induction of orchiectomy (ORCD) without ligation of any arteries or veins or removal of the testis and epididymis; 2) a control + Res-treated group (Con+Res): underwent sham surgery similar to the control, but was then treated with Res, as described below; 3) an ORCD-induced group: bilateral ORCD surgery as described above, and 4) a ORCD+Res-treated group: bilateral ORCD surgery followed by Res treatment. Res treatment began 4 weeks after ORCD and continued for 12 weeks. After 12 weeks, bone mineral density (BMD) and bone mineral content (BMC) were measured in the tibia and femur of each rat's right hind leg. Blood levels of bone turnover indicators such as deoxypyridinoline (Dpd), N-telopeptide of type I collagen (NTX I), alkaline phosphatase (ALP), and osteocalcin (OC), as well as receptor activator of nuclear factor kappa B (RANK) and osteoprotegerin (OPG) were assessed. RESULTS: ORCD significantly decreased BMD (P<0.01) and significantly increased bone resorption, manifested by increased RANK. In addition, it inhibited serum levels of OPG and OC. Res treatment after ORCD effectively increased serum levels of bone formation markers such as OPG and OC, compared with testisectomized rats (P<0.05). CONCLUSION Res could ameliorate bone loss induced by male hypogonadism, possible via restoration of the normal balance between RANK and OPG.
Rats ; Male ; Animals ; Bone Density ; Resveratrol/pharmacology* ; Osteoporosis ; Osteoprotegerin/pharmacology* ; Bone Remodeling ; Hypogonadism ; RANK Ligand/pharmacology*

The morbidity rate of medication-related osteonecrosis of the jaws (MRONJ) increased rapidly in recent years. Thusfar, the mechanism of MRONJ has no consensus. The possible mechanisms may include bone remodeling inhibition theory, angiogenesis inhibition theory, oral microorganism infection theory, immunosuppression theory, cytotoxicity-targeted oral epithelial cells, microcrack formation of maxillary or mandibular bone, and single nucleotide polymorphism. However, the efficacy of prevention and treatment based on a single mechanism is not ideal. Routine oral examination before MRONJ-related drug treatment, treatment of related dental diseases, and regular oral follow-up during drug treatment are of great significance for the prevention of MRONJ. During the treatment of MRONJ, the stage of MRONJ must be determined accurately, treatment must be standardized in accordance with the guidelines, and personalized adjustments must be made considering the specific conditions of patients. This review aimed to combine the latest research and guidelines for MRONJ and the experiences on the treatment of MRONJ in the Maxillofacial Surgery Department of West China Hospital of Stomatology, Sichuan University, and discuss the strategies to improve the clinical process.
Bisphosphonate-Associated Osteonecrosis of the Jaw/prevention & control* ; Bone Density Conservation Agents ; Bone Remodeling ; China ; Humans ; Jaw

The occurrence and development of pulmonary arterial hypertension (PAH) is closely related to the genetic mutation of bone morphogenetic protein receptor type II (BMPRII) encoding gene and the inflammatory response mediated by nuclear factor κB (NF-κB) pathway. This paper was aimed to investigate the effect of NF-κB pathway inhibitors on lipopolysaccharide (LPS)-induced pulmonary artery endothelial cell injury. Human pulmonary artery endothelial cells were treated with 1 μg/mL of LPS. The expression levels of BMPRII and interleukin-8 (IL-8) were detected by Western blot and qPCR. The rat PAH model was established by intraperitoneal (i.p.) injection of monocrotaline (MCT). The expression levels of BMPRII and IL-8 in pulmonary artery endothelial cells were detected by immunofluorescence staining. Cardiac hemodynamic changes and pulmonary vascular remodeling were detected in the MCT-PAH model rats. The results showed that LPS caused down-regulation of BMPRII expression and up-regulation of IL-8 expression in human pulmonary artery endothelial cells. NF-κB inhibitor BAY11-7082 (10 μmol/L) reversed the effect of LPS. In the pulmonary artery endothelial cells of MCT-PAH model, BMPRII expression was down-regulated, IL-8 expression was up-regulated, weight ratio of right ventricle to left ventricle plus septum [RV/(LV+S)] and right ventricular systolic pressure (RVSP) were significantly increased, cardiac output (CO) and tricuspid annular plane systolic excursion (TAPSE) were significantly reduced, and pulmonary vessel wall was significantly thickened. BAY11-7082 (5 mg/kg, i.p., 21 consecutive days) reversed the above changes in the MCT-PAH model rats. These results suggest that LPS down-regulates the expression level of BMPRII through NF-κB signaling pathway, promoting the occurrence and development of PAH. Therefore, the NF-κB pathway can be used as a potential therapeutic target for PAH.
Animals ; Bone Morphogenetic Protein Receptors, Type II ; Down-Regulation ; Endothelial Cells/metabolism* ; Humans ; Hypertension, Pulmonary/drug therapy* ; Lipopolysaccharides ; NF-kappa B/metabolism* ; Rats ; Rats, Sprague-Dawley ; Vascular Remodeling

In order to evaluate the biomechanical stability of titanium alloy screw with different structural parameters under bone remodeling, some three-dimensional finite element models were established and the bone remodeling process after implanting the screw was simulated. Three-dimensional finite element models consist of bone and screw with different lengths and diameters. Bone remodeling process was simulated by user-defined subroutine. It is found that the stress on the bone is concentrated on the groove and root of the internal thread. The screw stress is mainly on the beginning of the thread, and the whole stress decreases along the long axis of the screw. The stress distribution trend of bone and screw did not change significantly during the bone remodeling. The maximum equivalent stress value was different, the maximum equivalent stress on the screw and cancellous bone increased while the maximum equivalent stress value on the cortical bone decreased.
Biomechanical Phenomena ; Bone Remodeling ; Bone Screws ; Finite Element Analysis ; Stress, Mechanical ; Titanium

BACKGROUND: We investigated the clinical outcome in patients whose cavitary bone defects were treated with beta-tricalcium phosphate (β-TCP) after surgical removal of benign tumors. METHODS: Between March 2015 and December 2015, 20 patients who underwent operation for bone tumors were enrolled into this study and prospectively followed up for a median period of 28.1 months. RESULTS: When the radiographic sign of complete resorption was defined as greater than 50% resorption of the allograft material accompanied by bone remodeling until 12 months, 55% of patients had complete resorption. Positive correlation between the filling volume and time needed for complete resorption was not found (p = 0.184). CONCLUSIONS: Purified β-TCP could be a suitable choice as a bone graft substitute after the removal of benign bone tumors.
Allografts ; Bone Remodeling ; Bone Transplantation ; Humans ; Prospective Studies ; Transplants

PURPOSE: Bone markers can be useful for the diagnosis and treatment of skeletal diseases in children and adolescents. Owing to high skeletal growth velocity and rapid bone turnover, children and adolescents have higher bone marker levels than adults. Thus, a valid age- and sex-specific reference should be established for pediatric populations living in similar environments. We aimed to assess the associations of procollagen type I N-terminal propeptide (P1NP) and osteocalcin with age and sex in a group of healthy Korean children and adolescents. MATERIALS AND METHODS: The participants (290 boys and 290 girls, age range 0–18 years) were Korean outpatients. Serum P1NP and osteocalcin levels were measured in control materials and patient samples by electrochemiluminescence immunoassay using an automated Cobas e411 analyzer. RESULTS: Significant age-dependent variations in bone marker levels were observed in both sexes (p<0.001). The highest P1NP levels were observed during the first year of life; thereafter, levels decreased until puberty. There was no postnatal peak for osteocalcin; however, its levels remained higher than the adult reference range throughout childhood. Significant differences were observed between boys and girls (p<0.05), especially between the ages of 12 and 17 years. Cobas e411 results for P1NP showed satisfactory precision and linearity. CONCLUSION: We established reference data for P1NP and osteocalcin levels in healthy Korean children and adolescents, as the first and only study of these parameters in pre-adulthood in Korea. Cobas e411-quantified bone markers may be useful for determining bone metabolism indices.
Adolescent ; Adult ; Bone Remodeling ; Child ; Collagen Type I ; Diagnosis ; Female ; Humans ; Immunoassay ; Korea ; Metabolism ; Osteocalcin ; Outpatients ; Procollagen ; Puberty ; Reference Values

PURPOSE: This study evaluated differences in bone healing and remodeling among 3 implants with different surfaces: sandblasting and large-grit acid etching (SLA; IS-III Active®), SLA with hydroxyapatite nanocoating (IS-III Bioactive®), and SLA stored in sodium chloride solution (SLActive®). METHODS: The mandibular second, third, and fourth premolars of 9 dogs were extracted. After 4 weeks, 9 dogs with edentulous alveolar ridges underwent surgical placement of 3 implants bilaterally and were allowed to heal for 2, 4, or 12 weeks. Histologic and histomorphometric analyses were performed on 54 stained slides based on the following parameters: vertical marginal bone loss at the buccal and lingual aspects of the implant (b-MBL and l-MBL, respectively), mineralized bone-to-implant contact (mBIC), osteoid-to-implant contact (OIC), total bone-to-implant contact (tBIC), mineralized bone area fraction occupied (mBAFO), osteoid area fraction occupied (OAFO), and total bone area fraction occupied (tBAFO) in the threads of the region of interest. Two-way analysis of variance (3 types of implant surface×3 healing time periods) and additional analyses for simple effects were performed. RESULTS: Statistically significant differences were observed across the implant surfaces for OIC, mBIC, tBIC, OAFO, and tBAFO. Statistically significant differences were observed over time for l-MBL, mBIC, tBIC, mBAFO, and tBAFO. In addition, an interaction effect between the implant surface and the healing time period was observed for mBIC, tBIC, and mBAFO. CONCLUSIONS: Our results suggest that implant surface wettability facilitates bone healing dynamics, which could be attributed to the improvement of early osseointegration. In addition, osteoblasts might become more activated with the use of HA-coated surface implants than with hydrophobic surface implants in the remodeling phase.
Animals ; Bicuspid ; Bone Remodeling ; Bone-Implant Interface ; Dogs ; Durapatite ; Miners ; Osseointegration ; Osteoblasts ; Sodium Chloride ; Wettability