OBJECTIVE: To investigate the effects of continuous pumping of teriparatide (TPTD) on bone metabolism in ovariectomized and normal mice and provide experimental evidence for the selection of animal models for studying the effects of TPTD and its related peptides on osteoclasts. METHODS: Twenty-four female C57BL mice (6-weeks old) were subjected to ovariectomy (OVX) or sham operation followed 7 days later by continuous pumping of TPTD or the solvent vehicle (VEH) a micropump (SHAM-VEH, SHAM-TPTD, OVX-VEH, and OVX-TPTD groups; =6). Two weeks later, the tibial and femoral bones were harvested for micro-CT scanning to measure the parameters of the tibia and the femoral cortical bone. Histopathological examinations of the tibial tissue were conducted using HE staining and TRAP staining and the number of osteoclasts and the growth plate thickness were determined. The serum Ca2 + levels of the mice were measured. The primary osteoblasts from the cranial bone were treated with estradiol (E2) and TPTD for 48 h, and the expressions of β-catenin and RANKL protein in the cells were analyzed. RESULTS: The trabecular bone mass of OVX mice was significantly lower than that of sham-operated mice ( < 0.05). Continuous TPTD pumping significantly reduced tibial cancellous bone mass and femoral cortical bone area in the sham-operated mice, while in the castrated mice, TPTD pumping increased the cancellous bone mass without changing the cortical bone area. TRAP staining showed that cancellous osteoblasts in the tibia increased significantly in the castrated mice as compared with the sham-operated mice, and TPTD pumping significantly increased the number of cancellous osteoblasts in the sham-operated mice ( < 0.05). In the primary cultured osteoblasts, treatment with both E2 and TPTD obviously lowered the expression of β-catenin and increased the expression of RANKL as compared with TPTD treatment alone. CONCLUSIONS Continuous pumping of TPTD promotes bone resorption in normal mice but does not produce obvious bone resorption effect in the ovariectomized mice, suggesting that castrated mice are not suitable models for studying the effect of TPTD and the related peptides on the osteoclasts.
Animals ; Bone Density ; Bone Density Conservation Agents ; administration & dosage ; pharmacology ; Bone Resorption ; drug therapy ; Bone and Bones ; drug effects ; metabolism ; Female ; Growth Plate ; drug effects ; Mice ; Mice, Inbred C57BL ; Osteoclasts ; drug effects ; Ovariectomy ; RANK Ligand ; metabolism ; Teriparatide ; administration & dosage ; pharmacology ; beta Catenin ; metabolism

Anticonvulsants ; adverse effects ; Bone and Bones ; drug effects ; metabolism ; Calcium, Dietary ; administration & dosage ; Humans ; Valproic Acid ; adverse effects ; Vitamin D ; administration & dosage

Adolescent ; Anticonvulsants ; adverse effects ; Bone and Bones ; drug effects ; metabolism ; Calcium ; blood ; Calcium, Dietary ; administration & dosage ; Child ; Child, Preschool ; Dietary Supplements ; Epilepsy ; drug therapy ; metabolism ; Female ; Humans ; Male ; Valproic Acid ; adverse effects ; Vitamin D ; administration & dosage

OBJECTIVETo further investigate the {ptin vitro} effects of an osteoprotective herbal formula "ELP" (Herba Epimedii, Fructus Ligustri Lucidi and Fructus Psoraleae) using seropharmacological approach.

METHODSRats were fed with ELP or its individual component herbs for 2 days. The serum containing the postabsorbed ingredients of the herbal items were collected for cell culture using UMR106 cell, RAW264.7 cell and mesenchymal stem cell (MSC) isolated from the bone marrow of the rats. The effects of the herbal-containing serum on cell toxicity were detected by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assay; bromodeoxyuridine assay was conducted to measure the cell proliferation of UMR106 cell and MSC; cell activity was measured using colorimetric method, and mRNA expression of runt-related transcription factor 2 (Runx2), alkaline phosphatase (ALP) and osteopontin (OPN) of UMR106 and MSC as well as matrix metalloproteinase 9 (MMP-9), tartrate-resistant acid phosphatase (TRAP) and cathepsin K of RAW264.7 were analyzed using real-time reverse-transcription polymerase chain reaction.

RESULTSELP and its component serum exhibited no cytotoxic effects on the cells. The ELP-containing serum increased the proliferation of UMR106 cell and MSC by 25.7% and 14.4 %, respectively and the alkaline phosphatase activity of MSC was increased by 42.6%. On the contrary, it inhibited the RAW264.7 cell differentiation by 29.2 %. ELP serum upregulated the Runx2 expression of UMR and MSC by 1.18 fold and 1.27 fold, respectively. It also upregulated ALP and OPN expression in MSC by 1.69- and 2.12-fold, respectively. On the other hand, ELP serum down-regulated MMP-9 and cathepsin K expression of RAW264.7 cell by 0.46- and 0.36-fold, respectively.

CONCLUSIONSThe serum of the animals fed with ELP contains active ingredients which are effective in promoting osteogenesis and inhibiting osteoclastogenesis.

Absorption, Physiological ; drug effects ; Animals ; Bone and Bones ; drug effects ; pathology ; Cell Differentiation ; drug effects ; Cell Proliferation ; drug effects ; Cell Survival ; drug effects ; Drugs, Chinese Herbal ; pharmacology ; Male ; Mice ; Osteoclasts ; drug effects ; metabolism ; pathology ; Osteogenesis ; drug effects ; Protective Agents ; pharmacology ; RAW 264.7 Cells ; RNA, Messenger ; genetics ; metabolism ; Rats ; Rats, Sprague-Dawley ; Real-Time Polymerase Chain Reaction ; Serum ; metabolism

Objective: To evaluate the application of mechanically reinforced 45S5 Bioglass^®-derived glass ceramic porous scaffolds for repair of bone defect in rabbits. Methods: The BG-ZnB powders were added into the 45S5 Bioglass^® powder/paraffin microsphere mixtures and were sintered at 900℃ to obtain porous scaffolds with highly bioactive BG-ZnB of 0%, 2% or 4% of mass fraction (denoted as 45S5/ZnB0, 45S5/ZnB2, 45S5/ZnB4). Phase composition, porosity and compression properties of three kinds of as-sintered scaffolds were characterized by X-ray analysis, mercury porosimetry, and mechanical test. Thirty-six male New Zealand rabbits with critical-sized femoral bone defects were randomly divided into three groups (45S5/ZnB0 group, 45S5/ZnB2 group and 45S5/ZnB4 group, 12 for each), and were implanted with three kinds of porous scaffolds respectively. X-ray, micro-CT three-dimensional reconstruction and tissue slice staining were used to detected the efficiency of bone regeneration at 6 and 16 weeks after operation. The growth of newly formed bone was observed using HE, Masson staining and EnVision method. Results: Phase compositions of 45S5/ZnB2 and 45S5/ZnB4 were the same with 45S5/ZnB0, but the average pore size and porosity of the scaffolds were decreased with the increase of BG-ZnB content. 45S5/ZnB2 and 45S5/ZnB4 scaffolds exhibited higher compressive strength, osteogenesis and trabecular density than those of the 45S5/ZnB0 scaffold (all P<0.05). With the mechanical reinforcement of BG-ZnB increased, the content of new bone, collagen type I and osteocalcin increased. Conclusion: Low-melt BG-ZnB-assisted sintering is a promising approach to improve the mechanical strength of 45S5 Bioglass^®.
Animals ; Bone and Bones ; drug effects ; physiology ; Ceramics ; chemistry ; Glass ; Male ; Porosity ; Rabbits ; Tissue Scaffolds ; chemistry

Objective: To investigate the effect of resveratrol on peak bone mineral density and bone mass in growing rats. Methods: Thirty-six female healthy Wistar rats were randomly divided into control group, icariin group and resveratrol group with 12 rats in each group. Icariin (25 mg·kg^-1·d^-1), resveratrol (8.4 mg·kg^-1·d^-1) or equal volume of distilled water were given by gavage to icariin group, resveratrol group and control group, respectively. The rats were sacrificed after 12 weeks. The organ indexes were calculated and pathology sections were observed; the bone mineral density (BMD), bone biomechanics, serum bone metabolism index, and results of micro-CT scan were analyzed. Results: During the experiment, the body weight of rats showed an increasing trend and there was no significant difference among three groups (P0.05). There were no significant differences in organ index of vital organs and pathological changes among the groups (all P0.05). Compared with the control group, the whole body BMD, and the BMDs of femur and vertebrae in icariin and resveratrol groups were significantly increased after 12 weeks (all P<0.05). The maximum load values of femur and vertebrae, as well as elastic modulus of vertebrae in icariin and resveratrol groups were significantly higher than those in control group (P<0.05 or P<0.01). Micro-CT scan showed that the volumetric BMD, number of trabecular, trabecular thickness and bone volume/tissue volume of the cancellous bone in icariin and resveratrol groups were significantly higher and the trabecular separation was significantly lower than those in the control group (P<0.05 or P<0.01); while there was no significant difference in volumetric BMD of cortical bone for femur. The contents of osteocalcin in icariin and resveratrol groups were significantly higher than those in control group (all P<0.05), while the contents of tartarte-resistant acid phosphatase 5b (TRACP5b) were significantly lower than those in control group (all P<0.05).Conclusion: Resveratrol can inhibit bone resorption and enhance bone formation, so as to improve the peak bone mass and bone density, enhance bone strength and improve the microstructure of bone tissue in young rats.
Animals ; Bone Density ; drug effects ; Bone and Bones ; diagnostic imaging ; drug effects ; Female ; Femur ; drug effects ; Osteocalcin ; genetics ; metabolism ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Rats, Wistar ; Resveratrol ; pharmacology ; Tartrate-Resistant Acid Phosphatase ; genetics ; metabolism

Flavonoid naringin is widely distributed in various types of plants and is an important component of herbal Drynaria. In previous studies, Drynaria has been demonstrated to have inhibitory effects on inflammatory responses and bone destruction and exert anabolic effects on bone, has been widely used in the clinical treatment. Naringin, was in the stage of experimental yet. The experimental results have confirmed that naringin suppressed inflammation including arthritis by lowering the expression of inflammatory cytokines, and the mechanism can be explained as reducing the expression of NF-κB. Naringin has been shown to increase osteoblast proliferation by increasing the expression of BMP-2, inhibit osteoclast activity by reducing the expression of RANKL. In animal experimental, naringin was useful for osteoporosis, and the mechanisms are in-depth studies. Research in the field of traditional Chinese medicine and orthopedics, naringin as a explicit material structure in the components of Drynaria, has been concerned about the experimental studies, it is not only prosperity the development of traditional Chinese medicine research,but also ready for clinical studies anti-inflammatory and bone effects of naringin in the future.
Animals ; Anti-Inflammatory Agents ; pharmacology ; Bone and Bones ; drug effects ; Flavanones ; pharmacology ; Humans ; Medicine, Chinese Traditional ; Osteoblasts ; drug effects ; Osteoclasts ; drug effects ; Osteoporosis ; drug therapy ; Polypodiaceae ; chemistry

OBJECTIVETo investigate the protective effects of a Chinese herbal formula, taikong yangxin prescription (TKYXP) against bone deterioration in a hindlimb unloaded (tail-suspension) rat model.

METHODSThirty-two male Sprague-Dawley rats were divided into 4 groups: tail-suspension group fed with 2.5 g•kg(-1)•day(-1) of TKYXP extract (high dose), tail-suspension group fed with 1.25 g•kg(-1)•day(-1) (low dose), tail-suspended group treated with water placebo (placebo control group) and non tail-suspended group. The effects of TKYXP on bone were assessed using peripheral quantitative computed tomography (pQCT), microcomputerized tomography (micro-CT) and three-point bending biomechanical test on the femur in vivo.

RESULTSTKYXP had a significant protective effect against bone loss induced by tail-suspension on day 28, as shown in the reduction in bone mineral density (BMD) loss, preservation of bone micro-architecture and biomechanical strength. The administration ofhigh dose TKYXP could significantly reduce the total BMD loss by 4.8% and 8.0% at the femur and tibia regions, respectively, compared with the placebo control group (P<0.01) on day 28. Its bone protective effect on the femur was further substantiated by the increases of the trabecular BMD (by 6.6%), bone volume fraction (by 20.9%), trabecular number (by 9.5%) and thickness (by 11.9%) as compared with the placebo control group.

CONCLUSIONTKYXP may protect the bone under weightless influence from gradual structural deterioration in the tail-suspension model.

Animals ; Biomechanical Phenomena ; drug effects ; Bone Density ; drug effects ; Bone and Bones ; diagnostic imaging ; drug effects ; Drugs, Chinese Herbal ; administration & dosage ; pharmacology ; Femur ; Male ; Rats ; Rats, Sprague-Dawley ; Tibia ; Tomography Scanners, X-Ray Computed ; Weightlessness ; X-Ray Microtomography

BACKGROUND/AIMS: Proton pump inhibitors (PPIs) act by irreversibly binding to the H+-K+-ATPase of the proton pump in parietal cells and may possibly affect the vacuolar H+-ATPase in osteoclasts. METHODS: We investigated the effect of 8 weeks of PPI treatment on the parameters of bone turnover and compared PPI with revaprazan, which acts by reversibly binding to H+-K+-ATPase in proton pumps. This study was a parallel randomized controlled trial. For 8 weeks, either a PPI or revaprazan was randomly assigned to patients with gastric ulcers. The parameters of bone turnover were measured at the beginning of and after the 8-week treatment period. RESULTS: Twenty-six patients (PPI, n=13; revaprazan, n=13) completed the intention-to-treat analysis. After the 8-week treatment period, serum calcium and urine deoxypyridinoline (DPD) were increased in the PPI group (serum calcium, p=0.046; urine DPD, p=0.046) but not in the revaprazan group. According to multivariate linear regression analysis, age > or =60 years was an independent predictor for the changes in serum calcium and urine DPD. CONCLUSIONS: In elderly patients, administering a PPI for 8 weeks altered bone parameters. Our study suggested that PPIs might directly alter bone metabolism via the vacuolar H+-ATPase in osteoclasts.
Aged ; Amino Acids/drug effects/urine ; Bone Remodeling/*drug effects ; Bone and Bones/*metabolism ; Calcium/blood ; Female ; Humans ; Intention to Treat Analysis ; Linear Models ; Male ; Middle Aged ; Multivariate Analysis ; Osteoclasts/*metabolism ; Prospective Studies ; Proton Pump Inhibitors/*pharmacology ; Pyrimidinones/*pharmacology ; Tetrahydroisoquinolines/*pharmacology

The therapeutic effects and mechanisms of traditional Chinese kidney-tonifying drugs in treating osteoporosis have become the focus under study. Pharmacological studies have shown that traditional Chinese kidney-tonifying drugs are promoters for the proliferation of osteoblasts, inhibitors for the activity of osteoclasts, regulators for the estrogen level and its receptor, plays important roles in promoting osteogenesis and suppressing adipogenesis of marrow mesenchymal stem cells (MSCs), modulating the function of OPG/RANK/RANKL system and the metabolism of calcium and phosphorus, as well as antioxidation. The anti-osteoporotic active ingredients and pharmacological action mechanism of traditional Chinese kidney-tonifying drugs are summarized from the perspective of molecular and cell biology in this paper, so as to provide references for the study of their mechanism of anti-osteoporosis and for the development of traditional Chinese kidney-tonifying and bone-strengthening drugs.
Animals ; Bone and Bones ; drug effects ; physiopathology ; Drugs, Chinese Herbal ; pharmacology ; Humans ; Kidney ; drug effects ; physiopathology ; Osteoporosis ; drug therapy ; physiopathology