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Cinnamomum burmanini Blume increases bone turnover marker and induces tibia's granule formation in ovariectomized rats.

ABSTRACT: 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.

SUBMITTER: Kania N

PROVIDER: S-EPMC5884038 | biostudies-literature | 2018 Jan - Mar

REPOSITORIES: biostudies-literature

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Cinnamomum burmanini Blume increases bone turnover marker and induces tibia's granule formation in ovariectomized rats.

Kania Nia N Widowati Wahyu W Dewi Firli Rahmah Primula FRP Christianto Antonius A Setiawan Bambang B Budhiparama Nicolaas N Noor Zairin Z

Journal of Ayurveda and integrative medicine 20171202 1

<h4>Background</h4>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.<h4>Objective</h4>This study was aimed to investigate the effect of C. burmanini Blume on bone turnover marker, mineral elements, and mesostructure of ovariectomized rats.<h4>Materials and methods</h4>Thirty fe ...[more]

PMID: 29198835

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Project description:Postmenopausal osteoporosis is often treated with bisphosphonates (eg, alendronate, [ALN]), but oversuppression of bone turnover by long-term bisphosphonate treatment may decrease bone tissue heterogeneity. Thus, alternate treatment strategies after long-term bisphosphonates are of great clinical interest. The objective of the current study was to determine the effect of intermittent parathyroid hormone (PTH) following 12 weeks of ALN (a bisphosphonate) treatment in 6-month-old, ovariectomized (OVX) rats on bone microarchitecture, bone remodeling dynamics, and bone mechanical properties at multiple length scales. By using in vivo ?CT and 3D in vivo dynamic bone histomorphometry techniques, we demonstrated the efficacy of PTH following ALN therapy for stimulating new bone formation, and increasing trabecular thickness and bone volume fraction. In healthy bone, resorption and formation are coupled and balanced to sustain bone mass. OVX results in resorption outpacing formation, and subsequent bone loss and reduction in bone tissue modulus and tissue heterogeneity. We showed that ALN treatment effectively reduced bone resorption activity and regained the balance with bone formation, preventing additional bone loss. However, ALN treatment also resulted in significant reductions in the heterogeneity of bone tissue mineral density and tissue modulus. On the other hand, PTH treatment was able to shift the bone remodeling balance in favor of formation, with or without a prior treatment with ALN. Moreover, by altering the tissue mineralization, PTH alleviated the reduction in heterogeneity of tissue material properties induced by prolonged ALN treatment. Furthermore, switching to PTH treatment from ALN improved bone's postyield mechanical properties at both the whole bone and apparent level compared to ALN alone. The current findings suggest that intermittent PTH treatment should be considered as a viable treatment option for patients with prior treatment with bisphosphonates. © 2017 American Society for Bone and Mineral Research.

Project description:Bisphosphonates (BPs) and teriparatide (TPTD) are both effective treatments for osteoporosis, but BP treatment prior to daily TPTD treatment has been shown to impair the effect of TPTD in some clinical studies. In contrast, the loss of bone mineral density (BMD) that occurs after withdrawal of TPTD can be prevented by BP treatment. Although various studies have investigated the combination and/or sequential use of BP and TPTD, there have been no clinical studies investigating sequential treatment with zoledronic acid (ZOL) and TPTD (or vice versa). In this study, we evaluated the effects of sequential treatment with TPTD followed by ZOL, and ZOL followed by TPTD, using ovariectomized (OVX) rats. Two months after OVX, osteopenic rats were treated with ZOL, TPTD, or vehicle for a period of 4 months (first treatment period), and then the treatments were switched and administered for another 4 months (second treatment period). The group treated with ZOL followed by TPTD showed an immediate increase in BMD of the proximal tibia and greater BMD and bone strength of the lumbar vertebral body, femoral diaphysis, and proximal femur than the group treated with ZOL followed by vehicle. Serum osteocalcin, a marker of bone formation, increased rapidly after switching to TPTD from ZOL. The group treated with TPTD followed by ZOL did not lose BMD in the proximal tibia after TPTD was stopped, while the group treated with TPTD followed by vehicle did lose BMD. The BMD and bone strength of the lumbar vertebral body, femoral diaphysis, and proximal femur were greater in the group treated with TPTD followed by ZOL than in the group treated with TPTD followed by vehicle. The increase in serum osteocalcin and urinary CTX after withdrawal of TPTD was prevented by the switch from TPTD to ZOL. In conclusion, our results demonstrate that switching from ZOL to TPTD resulted in a non-attenuated anabolic response in the lumbar spine and femur of OVX rats. In addition, switching from TPTD to ZOL caused BMD to be maintained or further increased. If these results can be reproduced in a clinical setting, the sequential use of ZOL followed by TPTD or vice versa in the treatment of osteoporosis patients would contribute to increases in BMD that, hopefully, would translate into a corresponding decrease in the incidence of vertebral and non-vertebral fractures.

Project description:Osteoporosis (OP) is a systemic skeletal disorder, manifesting with a reduction in bone mass and deterioration of the microarchitecture. Mesenchymal stem cells (MSCs) have an innate ability to differentiate into several cell types, including osteoblasts (OB). Ginsenoside Rb1 (GRb1) is an ethanol extract from ginseng and contains a highly concentrated form of ginsenoside. GRb1 shows extensive beneficial health effects such as anti-oxidative and anti-inflammatory functions, modulating the immune system and inhibiting osteoclastogenesis. We hypothesized that GRb1 can promote MSC differentiation into OBs and inhibit bone loss. In the present study, we aimed to address two questions: (1) Will GRb1 have a positive effect on osteogenic differentiation of MSCs? and (2) Will GRb1 halt bone loss in ovariectomized (OVX) rats? We investigated the effects of GRb1 on viability and osteogenic differentiation of rat mesenchymal stem cells (rMSCs). Our results showed that GRb1 at concentrations of 10-8 M and 10-6 M can increase alkaline phosphatase activity, mineralization and the expression of osteogenic related proteins, such as osteopontin and osteoprotegerin, while incubating rMSCs with osteogenic induction medium and GRb1. Adding GRb1 into the medium can prevent rMSCs from Oxidative damage at the concentration of 25?M H2O2. Furthermore, 40 4-month-old rats were assigned to 5 groups(8 rats per group): the basal group, the sham group, the OVX group, the high dose of GRb1 group (6 mg/kg/day) and the low dose of GRb1 group (3 mg/kg/day). Rats recrived treatment 3days after surgery and last for 14 weeks. Examinations included serum analysis, mechanical testing, Masson-Goldner trichrome staining and bone histomorphometry analysis. The results showed that OVX can lead to dyslipidemia and excessive oxidative stress, whereas GRb1 cannot significantly halt dyslipidemia and excessive oxidative stress in OVX rats. In addition, the bone density of the lumbar vertebra and femur were decreased significantly in the OVX rats, and GRb1 could not inhibit bone loss. Bone histomorphometry analysis showed that the number and width of bone trabecula of the tibia were reduced in OVX rats, and GRb1 could not prevent their occurrence. A bone biomechanics assay showed that GRb1 cannot improve the ability of bone structure to resist fracture of the femur in OVX rats. The current study demonstrated that GRb1 has an obvious effect on osteogenic differentiation in rMSCs but no obvious effect on bone loss in OVX rats. These findings indicate GRb1 has a positive effect on rMSCs but does not have an effect on bone loss in OVX rats at the concentration we used.

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Cinnamomum burmanini Blume increases bone turnover marker and induces tibia's granule formation in ovariectomized rats.

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Cinnamomum burmanini Blume increases bone turnover marker and induces tibia's granule formation in ovariectomized rats.

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