Effects of tanshinol on markers of bone turnover in ovariectomized rats and osteoblast cultures.
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ABSTRACT:
SUBMITTER: Han J
PROVIDER: S-EPMC5528899 | biostudies-other | 2017
REPOSITORIES: biostudies-other
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Project description:Surgical methods for accelerating orthodontic tooth movement are limited by possible damage to the tooth root and patient discomfort. 4-Hexylresorcinol (4HR) has been shown to increase bone remodeling and may potentially facilitate tooth movement. This study investigated the (1) effect of 4HR administration on osteoblast-like cells and (2) effect of 4HR administration on tooth movement in ovariectomized rats. Saos-2 cells were treated with either 4HR or solvent (control). Protein expression levels were investigated 2, 8, and 24 h after treatment. Thirty ovariectomized Sprague-Dawley rats were divided into two experimental groups (A and B) and one control group. After installation of an orthodontic tooth movement device, groups A and B received subcutaneous weekly injections of 4HR (1.28 and 128 mg/kg). Micro-computerized tomography and histological analyses were performed after 2 weeks of tooth movement. The application of 4HR elevated expression of osteogenic markers in Saos-2 cells. Movement of the first molars was significantly greater in rats administered 4HR. Furthermore, the expression of bone morphogenic protein-2, receptor activator of nuclear factor kappa-B ligand, osteocalcin, and tartrate-resistant acid phosphatase were increased after 4HR administration. 4HR application demonstrated increased expression of osteogenic markers in Saos-2 cells and accelerated orthodontic tooth movement in rats.
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Project description:BACKGROUND:Bone fragility and an increase in susceptibility to fracture osteoporosis is characterized by a reduction in bone mass and the micro-architectural deterioration of bone tissue. There is no previous study regarding the effect of Cinnamomum burmanini Blume on osteoporosis. OBJECTIVE:This study was aimed to investigate the effect of C. burmanini Blume on bone turnover marker, mineral elements, and mesostructure of ovariectomized rats. MATERIALS AND METHODS:Thirty female Wistar rats were randomly divided into five groups, which included a control group (sham surgery), ovariectomy group (OVX), and ovariectomy groups in the presence of ethanolic extract of C. burmanini Blume (EECB) at doses of 12.5; 25; 50 mg/kg body weight (BW). Analysis of serum C-telopeptide collagen type I (CTX) and osteocalcin (OC) were done by enzyme-linked immunosorbent assay (ELISA). Tibia mineral elements and mesostructure were analyzed by X-ray Fluorescence and Scanning Electron Microscopy, respectively. In silico study was performed by modeling protein structure using SWISS-MODEL server and Ramachandran plot analysis. RESULTS:The increase in OC and CTX were significantly attenuated by treatments of EECB. Ovariectomy significantly decreased Cu/Zn ratio compared to sham-operated rats (p < 0.05). Mesostructure of ovariectomized rats was significantly different compared with the control group. CONCLUSION:Cinnamon was able to normalize bone turnover markers, but, the mesostructure of hydroxyapatite crystal growth was achieved at the highest dose extract. In silico study showed that the active compound of EECB could not only support osteoclastogenesis process by decreasing the binding energy between RANKL and RANK, but also by inhibiting the interaction between OPG and RANK.
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Project description:Inhibition of sclerostin with sclerostin antibody (Scl-Ab) results in stimulation of bone formation on cancellous (Cn), endocortical (Ec), and periosteal (Ps) surfaces in rodents and non-human primates. With long-term dosing of Scl-Ab, the increase in bone formation is not sustained, attenuating first on Cn surfaces and later on Ec and Ps surfaces. In Cn bone, the attenuation in bone formation (self-regulation) is associated with transcriptional changes in the osteocyte (OCy) that would limit mitogenesis and are sustained with continued dosing. The expression changes in Cn OCy occur coincident with a decrease in osteoprogenitor (OP) numbers that may directly or indirectly be a consequence of the transcriptional changes in the OCy to limit OP proliferation. To characterize the Scl-Ab-mediated changes in cortical (Ct) bone and compare these changes to Cn bone, densitometric, histomorphometric, and transcriptional analyses were performed on femur diaphyses from aged ovariectomized rats. Animals were administered 50?mg/kg/wk of Scl-Ab or vehicle for up to 6?months (183?days), followed by a treatment-free period (up to 126?days). Scl-Ab increased Ct mass and area through day 183, which declined slightly when treatment was discontinued. Ps and Ec bone formation was sustained through the dosing on both Ct surfaces, with evidence of a decline in bone formation only at day 183 on the Ec surface. This is in contrast to Cn bone, where reduced bone formation was observed after day 29. TaqMan analysis of 60 genes with functional roles in the bone using mRNA isolated from laser capture micro-dissection samples enriched for Ec osteoblasts and Ct OCy suggest a pattern of gene expression in Ct bone that differed from Cn, especially in the OCy, and that corresponded to observed differences in the timing of phenotypic changes. Notable with Scl-Ab treatment was a "transcriptional switch" in Ct OCy at day 183, coincident with the initial decline in bone formation on the endocortex. A consistent sustained increase of expression for most genes in response to Scl-Ab was observed from day 8 through day 85 at the times of maximal bone formation on both Ct surfaces; however, at day 183, this increase was reversed, with expression of these genes generally returning to control values or decreasing compared to vehicle. Genes exhibiting this pattern included Wnt inhibitors Sost and Dkk1, though both had been up-regulated until the end of dosing in Cn OCy. Changes in cell cycle genes such as Cdkn1a and Ndrg1 in Ct OCy suggested up-regulation of p53 signaling, as observed in Cn OCy; however, unlike in Cn bone, p53 signaling was not associated with decreased bone formation and was absent at day 183, when bone formation began to decline on the Ec surface. These data demonstrate involvement of similar molecular pathways in Ct and Cn bone in response to Scl-Ab but with a different temporal relationship to bone formation and suggest that the specific mechanism underlying self-regulation of Scl-Ab-induced bone formation may be different between Cn and Ct bone.
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Project description:Deer sinew (DS) has been used traditionally for various illnesses, and the major active constituent is collagen. In this study, we assessed the effects of collagen peptide from DS on bone loss in the ovariectomized rats. Wister female rats were randomly divided into six groups as follows: sham-operated (SHAM), ovariectomized control (OVX), OVX given 1.0 mg/kg/week nylestriol (OVX + N), OVX given 0.4 g/kg/day collagen peptide (OVX + H), OVX given 0.2 g/kg/day collagen peptide (OXV + M), and OVX given 0.1 g/kg/day collagen peptide (OXV + L), respectively. After 13 weeks of treatment, the rats were euthanized, and the effects of collagen peptide on body weight, uterine weight, bone mineral density (BMD), serum biochemical indicators, bone histomorphometry, and bone mechanics were observed. The data showed that BMD and concentration of serum hydroxyproline were significantly increased and the levels of serum calcium, phosphorus, and alkaline phosphatase were decreased. Besides, histomorphometric parameters and mechanical indicators were improved. However, collagen peptide of DS has no effect on estradiol level, body weight, and uterine weight. Therefore, these results suggest that the collagen peptide supplementation may also prevent and treat bone loss.
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Project description:The clinical utility of Traditional Chinese Medicine (TCM) herbs/roots extracts in osteoporosis (OP) and osteoarthritis (OA) has been described in multiple reports, but there have been few studies of TCM for preventing bone loss and cartilage degradation simultaneously. Six-month-old female Sprague-Dawley rats each were subjected to ovariectomized (OVX) or sham surgery and treated orally once daily with herbal extracts or vehicle. Body weight was recorded weekly, and blood samples were collected from fasting animals at different time points. Biochemical markers of bone resorption and cartilage degradation were analyzed. Changes in bone mineral density and calcium content were determined in the femoral center and femoral telocentric end of rats. Out of 56 TCM herbs/roots extracts, only kudzu root demonstrated consistent joint protective effects. OVX resulted in a marked increase in bone resorption and cartilage degradation, which could be significantly reversed by kudzu after three weeks of treatment. Compared to vehicle, kudzu induced a significant increase in bone mineral density in the femoral center and femoral telocentric end, and calcium content. The results show that kudzu exerts direct effects on articular cartilage in the OVX rat and can effectively prevent the acceleration of cartilage degradation induced by ovariectomy. Moreover, kudzu has demonstrated positive effects on metabolic health (cause a weight reduction) and may represent a possible treatment for OP and OA with high body mass index. Further studies are needed to investigate the potential effects of kudzu root in postmenopausal women.
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Project description:BackgroundJSOG-6 is used as a traditional medicine to relieve the symptoms associated with inflammation, rheumatism, and osteoporosis in Korea. In the present study, we investigated the effects of JSOG-6 on bone loss prevention both in in vitro and in vivo as well as its underlying mechanism of action.MethodsProtection against bone loss was assessed in an ovariectomized (OVX) mouse model. Bone microarchitecture was measured using a micro-computed tomography to detect the parameters of three-dimensional structure of a trabecular bone. Serum biomarkers were also evaluated in an OVX-induced model. Osteoclasts derived from mouse bone marrow cells (BMCs) and osteoblastic MC3T3-E1 cells were also employed to investigate the mechanism of action.ResultsOral administration of JSOG-6 significantly increased the bone mineral density (BMD) of the femur in OVX mice in vivo. Especially, the reduced Tb.No (trabecular bone number) in the OVX group was significantly recovered by JSOG-6 treatment. The serum levels of alkaline phosphatase (ALP), osteocalcin, C-terminal telopeptide, and tartrate-resistant acid phosphatase, biomarkers of bone resorption, were significantly elevated in OVX mice, but JSOG-6 effectively inhibited the increase in OVX mice. JSOG-6 was also found to enhance the osteoblastic differentiation and maturation with the increase of the density and ALP activity, a marker of osteoblastic differentiation, as well as calcium deposition, a marker of osteoblastic maturation in MC3T3-E1 cells. The effects of JSOG-6 on osteoblastic differentiation were also associated in part with the increase of ALP and OPN mRNA expressions and the decrease of RANKL mRNA expression in MC3T3-E1 cells.ConclusionsThe findings demonstrate that JSOG-6 induced protection against bone loss in OVX mice, and its anti-osteoporotic property might be, in part, a function of the stimulation of osteoblast differentiation and the inhibition of osteoclast formation. These findings suggest that JSOG-6 might be an applicable therapeutic traditional medicine for the regulation of the osteoporotic response.
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Project description:Recently, a number of studies have demonstrated the potential beneficial role for novel anti-diabetic GLP-1 receptor agonists (GLP-1RAs) in the skeleton metabolism in diabetic rodents and patients. In this study, we evaluated the impacts of the synthetic GLP-1RA Liraglutide on bone mass and quality in osteoporotic rats induced by ovariectomy (OVX) but without diabetes, as well as its effect on the adipogenic and osteoblastogenic differentiation of bone marrow stromal cells (BMSCs). Three months after sham surgery or bilateral OVX, eighteen 5-month old female Wistar rats were randomly divided into three groups to receive the following treatments for 2 months: (1) Sham + normal saline; (2) OVX + normal saline; and (3) OVX + Liraglutide (0.6 mg/day). As revealed by micro-CT analysis, Liraglutide improved trabecular volume, thickness and number, increased BMD, and reduced trabecular spacing in the femurs in OVX rats; similar results were observed in the lumbar vertebrae of OVX rats treated with Liraglutide. Following in vitro treatment of rat and human BMSCs with 10 nM Liraglutide, there was a significant increase in the mRNA expression of osteoblast-specific transcriptional factor Runx2 and the osteoblast markers alkaline phosphatase (ALP) and collagen ?1 (Col-1), but a significant decrease in peroxisome proliferator-activated receptor ? (PPAR?). In conclusion, our results indicate that the anti-diabetic drug Liraglutide can exert a bone protective effect even in non-diabetic osteoporotic OVX rats. This protective effect is likely attributable to the impact of Liraglutide on the lineage fate determination of BMSCs.
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Project description:BACKGROUND:This study examined the effects of whey protein supplementation, compared with an isocaloric carbohydrate beverage and water, consumed immediately following an intense swimming trial on bone turnover in adolescent swimmers. METHODS:Fifty-eight (31 female, 27 male) swimmers (14.1?±?0.4?years) were stratified into three groups matched for age, sex and body mass. The protein and carbohydrate groups consumed two isocaloric post-exercise beverages each containing 0.3?g.kg-?1 of whey protein (with ~?6?mg of calcium) or maltodextrin while the control group consumed water. Participants provided a morning, fasted, resting blood sample, then performed an intense swimming trial consisting of a maximal 200?m swim followed by a high intensity interval swimming protocol (5x100m, 5x50m and 5x25m; 1:1 work-to-rest ratio). Following swimming, they consumed their first respective post-exercise beverage, and 2?h later, they performed a second maximal swim immediately followed by the second beverage. Approximately 3?h after the second beverage, two post-consumption blood samples were collected at 8?h and 24?h from baseline. Procollagen type 1 intact N-terminal propeptide (PINP) and carboxy-terminal collagen crosslinks (CTXI) were measured in serum. The multiples of medians of PINP and CTXI were also used to calculate bone turnover rate and balance. RESULTS:No significant changes were observed in PINP. CTXI increased (+?11%) at 8?h in all groups, but then significantly decreased (-?22%) at 24?h in the protein group only. The protein group also had a significantly higher calculated rate of bone turnover at 8?h and 24?h compared to baseline, which was not observed in the other groups. CONCLUSIONS:These results shed light on the potential importance of protein consumed shortly after intense swimming in promoting positive bone turnover responses up to 24?h following exercise in adolescent athletes. CLINICAL TRIAL REGISTRATION:ClinicalTrials.gov PRS; NCT04114045. Registered 1 October 2019 - Retrospectively registered.
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