Insufficient alveolar bone thickness increases the risk of periodontal dehiscence and fenestration, especially in orthodontic tooth movement. Abaloparatide (ABL), a synthetic analog of human PTHrP (1-34) and a clinical medication for treating osteoporosis, has recently demonstrated its potential in enhancing craniofacial bone formation. Herein, we show that intraoral submucosal injection of ABL, when combined with mechanical force, promotes in situ alveolar bone thickening. The newly formed bone is primarily located outside the original compact bone, implying its origin from the periosteum. RNA sequencing of the alveolar bone tissue revealed that the focal adhesion (FA) pathway potentially mediates this bioprocess. Local injection of ABL alone enhances cell proliferation, collagen synthesis, and phosphorylation of focal adhesion kinase (FAK) in the alveolar periosteum; when ABL is combined with mechanical force, the FAK expression is upregulated, in line with the accomplishment of the ossification. In vitro, ABL enhances proliferation, migration, and FAK phosphorylation in periosteal stem cells. Furthermore, the pro-osteogenic effects of ABL on alveolar bone are entirely blocked when FAK activity is inhibited by a specific inhibitor. In summary, abaloparatide combined with mechanical force promotes alveolar bone formation via FAK-mediated periosteal osteogenesis. Thus, we have introduced a promising therapeutic approach for drug-induced in situ alveolar bone augmentation, which may prevent or repair the detrimental periodontal dehiscence, holding significant potential in dentistry.
Osteogenesis/drug effects* ; Periosteum/cytology* ; Parathyroid Hormone-Related Protein/administration & dosage* ; Animals ; Focal Adhesion Protein-Tyrosine Kinases/metabolism* ; Alveolar Process/drug effects* ; Cell Proliferation/drug effects* ; Phosphorylation ; Rats ; Male ; Humans ; Focal Adhesion Kinase 1/metabolism* ; Cell Movement/drug effects*

Recent studies have shown that Er-Zhi-Wan (EZW), a traditional Chinese medicine consisting of Herba Ecliptae (HE) and Fructus Ligustri Lucidi (FLL), had a definite antiosteoporotic effect on osteoporotic femur, but its effect on osteoporosis of alveolar bone remains unknown. In the present study, we investigated the effects of Er-Zhi-Wan (EZW) on the microarchitecture and the regulation of Wnt/β-catenin signaling pathway in the alveolar bone of ovariectomized rats. Thirty Sprague-Dawley rats were randomly divided into three groups: sham operation group (sham, n=10), ovariectomy (OVX) group (n=10), and OVX with EZW treatment group (EZW group, n=10). From one week after ovariectomy, EZW (100 mg/mL) or vehicle (distilled water) was fed (1 mL/100 g) once per day for 12 weeks until the sacrifice of the rats. The body weights were measured weekly. After sacrifice, the sera and mandible were collected and routinely prepared for the measurement of alveolar trabecular microarchitecture, serum levels of E2, bone-specific alkaline phosphatase (BALP) and tartrate-resistant acid phosphatase 5b (TRAP5b), as well as mandibular mRNA expression of Wnt/β-catenin signaling pathway molecules wnt3a, low-density lipoprotein receptor-related protein 5 (LRP5), β-catenin and dickkopf homolog 1 (DKK1). The results showed that EZW treatment significantly prevented the body weight gain, degradation of alveolar trabecular microarchitecture and alveolar bone loss in the OVX rats. Furthermore, we observed that EZW could increase the serum levels of E2 and BALP, and decrease levels of serum TRAP5b in EZW group compared with vehicle group. In addition, RT-PCR results revealed that EZW upregulated the expression levels of wnt3a, LRP5 and β-catenin, and reduced the expression of DKK1 in OVX rats. Taken together, our results suggested that EZW may have potential anti-osteoporotic effects on osteoporotic alveolar bone by stimulating Wnt/LRP5/β-catenin signaling pathway.
Acid Phosphatase ; blood ; Alkaline Phosphatase ; blood ; Alveolar Process ; drug effects ; metabolism ; Animals ; Body Weight ; drug effects ; Drugs, Chinese Herbal ; pharmacology ; Estradiol ; blood ; Female ; Gene Expression ; drug effects ; Intercellular Signaling Peptides and Proteins ; genetics ; Isoenzymes ; blood ; Low Density Lipoprotein Receptor-Related Protein-5 ; genetics ; Mandible ; drug effects ; metabolism ; Medicine, Chinese Traditional ; methods ; Organ Size ; drug effects ; Ovariectomy ; Rats, Sprague-Dawley ; Reverse Transcriptase Polymerase Chain Reaction ; Tartrate-Resistant Acid Phosphatase ; Time Factors ; Up-Regulation ; drug effects ; Uterus ; drug effects ; growth & development ; Wnt Signaling Pathway ; drug effects ; genetics ; Wnt3A Protein ; genetics ; beta Catenin ; genetics

AIMTo determine the effect of local simvastatin application on the mRNA expression level of transforming growth factor-beta1 (TGF-beta1), bone morphogenetic protein-2 (BMP-2) and vascular endothelial growth factor (VEGF) in the tooth sockets of rat.

METHODOLOGYForty-eight male Wistar rats were randomly divided into experimental and control groups (n = 24). Polylactic acid/polyglycolic acid copolymer carriers, with or without simvastatin, were implanted into extraction sockets of right mandibular incisors. The expression of TGF-beta1, BMP-2 and VEGF mRNA was determined by in situ hybridization in the tooth extraction socket at five days, one week, two weeks and four weeks after implantation.

RESULTSThe fusiform stroma cells in the tooth extraction socket began to express TGF-beta1, BMP-2 and VEGF mRNA in both experimental and control groups from one week after tooth extraction until the end of experiment. The expression of TGF-beta1 and BMP-2 mRNA in the experimental group was significantly up-regulated after one, two and four weeks, and expression of VEGF mRNA was significantly increased after one and two weeks compared with that in the control group.

CONCLUSIONThe findings indicate that local administration of simvastatin can influence alveolar bone remodeling by regulating the expression of a school of growth factors which are crucial to osteogenesis in the tooth extraction socket.

Alveolar Process ; drug effects ; Animals ; Bone Morphogenetic Protein 2 ; analysis ; drug effects ; Bone Remodeling ; drug effects ; Drug Carriers ; Endothelial Cells ; drug effects ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; pharmacology ; In Situ Hybridization ; Lactic Acid ; Male ; Mandible ; drug effects ; Osteoblasts ; drug effects ; Osteogenesis ; drug effects ; Polyglycolic Acid ; RNA, Messenger ; analysis ; drug effects ; Random Allocation ; Rats ; Rats, Wistar ; Simvastatin ; pharmacology ; Stromal Cells ; drug effects ; Time Factors ; Tooth Socket ; drug effects ; Transforming Growth Factor beta1 ; analysis ; drug effects ; Up-Regulation ; drug effects ; Vascular Endothelial Growth Factor A ; analysis ; drug effects

The aim of this study was to evaluate the injectability, histocompatibility, function and other properties of the injectable bioactive bone repairing material of nano-hydroxyapatite and polyamide-66 (n-HA/PA66) composite. The XRD pattern, the relationship between the injectability and liquid-powder ratio, setting time and liquid-powder ratio, compressive strength and liquid-powder ratio were assessed. The size of the composite was determined to be 70 nm in length and 30 to 50 nm in width, and the molecular weight of polyamides-66 was 18000. The diameter of pores of the composite was about 200 to 400 micrometer. To evaluate the histocompatibility and function, 8 male dogs were studied with the injectable n-HA/PA66 composite implanted in the artificial defected alveolus of mandible on only one side to be compared with the intact alveolus on the other side. The specimens were taken at 4, 8, 12, 16 months after the implantation and the results were evaluated. The XRD pattern of the solidificated n-HA/PA66 composite was the same as the powdered n-HA/PA66 composite. The injectable n-HA/PA66 composite had a good injectability, 25 to 30 minutes setting time and about 37 MPa compressive strength when the liquid-powder ratio was 0.50. The healing of the gingiva was well at the implanted areas in all animals. The height of the repaired alveolar bone was obvious higher than that of the blank control. The earlier sign of ossification was histologically observed at 16 weeks after implantation. The injectable n-HA/PA66 composite has good biocompatibility and osteoconductive property. As an injectable material, with good maneuverability, it is useful for repairing irregular bone defects, especially in oral and maxillofacial surgery.
Alveolar Process ; drug effects ; physiology ; Animals ; Bone Regeneration ; drug effects ; physiology ; Bone Substitutes ; administration & dosage ; pharmacology ; Dogs ; Durapatite ; Injections ; Male ; Materials Testing ; Nylons ; Prosthesis Implantation ; methods ; X-Ray Diffraction