Astaxanthin prevents bone loss in osteoporotic rats with palmitic acid through suppressing oxidative stress.

OBJECTIVES: The study aimed to assess the role of Astaxanthin (ATX) in palmitic acid(PA) -induced bone loss in Ovariectomized(OVX) rats. METHODS: In the OVX rat model, we observed that PA affects bone metabolism and accelerates bone loss. Additionally, treatment with ATX was able to suppress the deleterious effects of PA and a simultaneous decrease in serum MDA levels and an increase in SOD was observed. RESULTS: In addition, rats treated with ATX were observed to have significantly increased bone mass and elevated activity of SIRT1 and SOD2 in bone tissue. When MC3T3-E1 and RAW264.7 cells induced osteoblast and osteoclast differentiation, the ATX intervention was able to significantly restore the restriction of osteogenic differentiation and the up-regulation of osteoclast differentiation with PA therapy. Furthermore, we confirm that PA damage to cells is caused by increased oxidative stress, and that ATX can target and modulate the activity of SIRT1 to regulate the levels of oxidative stress in cells. CONCLUSION: Summarizing, ATX may inhibit PA-induced bone loss through its antioxidant properties via the SIRT1 signaling pathway.

Niacin treatment prevents bone loss in iron overload osteoporotic rats via activation of SIRT1 signaling pathway.

Recently, more and more studies have revealed that iron overload can lead to osteoporosis by inducing oxidative stress. Niacin (NAN), also known as nicotinate or vitamin B3, has been confirmed to possess potent antioxidative effects. In addition, very little is currently known about the protective effects of NAN on iron overload in osteoporotic bone tissue. Therefore, we aimed to evaluate the protective effect of niacin on iron overload-induced bone injury and to investigate the effect and underlying mechanisms of the niacin and iron overload on intracellular antioxidant properties. When MC3T3-E1 and RAW264.7 cells were cultured in the presence of ammonium ferric citrate(FAC), NAN therapy could increase the matrix mineralization and promote expression of osteogenic markers in MC3T3-E1, inhibit osteoclastic differentiation of RAW264.7 cells, while increasing intracellular reactive oxygen species (ROS) levels and strengthening mitochondrial membrane potential (MMP). In the ovariectomized (OVX) rat model, NAN had an obvious protective effect against iron-overloaded injury. Meanwhile, superoxide dismutase 2 (SOD2), intracellular antioxidant enzymes and silent information regulator type 1 (SIRT1), were up-regulated in response to NAN exposures in MC3T3-E1. Furthermore, SIRT1 inhibitor EX527 attenuated the protective effects of NAN. Results revealed that NAN could stimulate osteogenic differentiation, inhibit osteoclastic differentiation and markedly increased antioxidant properties in cells through the induction of SIRT1. Studies suggest that niacin is a promising agent for preventing bone loss in iron overload conditions.

Local administration with tauroursodeoxycholic acid could improve osseointegration of hydroxyapatite-coated titanium implants in ovariectomized rats.

Despite advances in the pathogenesis of Tauroursodeoxycholic acid (TUDCA) on bone, the understanding of the effects and mechanisms of bone osseointegration in TUDCA-associated Hydroxyapatite (HA)-coated titanium implants remains poor. Therefore, the present work was aimed to evaluate the effect of local administration with TUDCA on HA-coated titanium implants osseointegration in ovariectomized(OVX) rats and further investigation of the possible mechanism. Twelve weeks after bilateral ovariectomy, all animals were randomly divided into three groups: sham operation(Sham) group, OVX group and TUDCA group, and all the rats from Sham group and OVX group received HA implants and animals belonging to group TUDCA received TUDCA-HA implants until death at 12 weeks. The bilateral femurs of rats were harvested for evaluation. TUDCA increased new bone formation around the surface of titanium rods and push-out force other than group OVX. Histology, Micro-CT and biochemical analysis results showed systemic TUDCA showed positive effects than OVX group on bone formation in osteopenic rats, with beneficial effect on via activation OPG/RANKL pathway and BMP-2/Smad1 pathway and microarchitecture as well as by reducing protein expression of TNF-α and IFN-γ. The present study suggests that local use of TUDCA may bring benefits to the osseointegration of HA-coated titanium implants in patients with osteoporosis, and this effect may be related to the inhibition of inflammatory reaction and promotion of osteogenesis.

Selenium-modified calcium phosphate cement can accelerate bone regeneration of osteoporotic bone defect.

OBJECTIVE: The purpose is to observe whether local administration with selenium (Se) can enhance the efficacy of calcium phosphate cement (CPC) in the treatment of osteoporotic bone defects. METHODS: Thirty ovariectomized (OVX) rats with two defects were generated and randomly allocated into the following graft study groups: (1) OVX group (n = 10), (2) CPC group (n = 10); and (3) Se-CPC group (n = 10). Then, these selenium-modified calcium phosphate cement (Se-CPC) scaffolds were implanted into the femoral epiphysis bone defect model of OVX rats for 12 weeks. Micro-CT, history, western blot and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analysis were used to observe the therapeutic effect and to explore the possible mechanism. RESULT: Micro-CT and histological analysis evaluation showed that the Se-CPC group presented the strongest effect on bone regeneration and bone mineralization when compared with the CPC group and the OVX group. Protein expressions showed that the oxidative stress protein expressions, such as SOD2 and GPX1 of the Se-CPC group, are significantly higher than those of the OVX group and the CPC group, while Se-CPC remarkably reduced the expression of CAT. RT-qPCR analysis showed that the Se-CPC group displayed more OPG than the OVX and CPC groups (p < 0.05), while Se-CPC exhibited less RANKL than the OVX and CPC groups (p < 0.05). CONCLUSION: Our current study demonstrated that Se-CPC is a scheme for rapid repair of femoral condylar defects, and these effects may be achieved by inhibiting local oxidative stress and through OPG/RANKL signaling pathway.

Local administration of aspirin with ß-tricalcium phosphate/poly-lactic-co-glycolic acid (ß-TCP/PLGA) could enhance osteoporotic bone regeneration.

Composite materials ß-tricalcium phosphate (ß-TCP) and poly-lactic-co-glycolic acid (PLGA) have achieved stable bone regeneration without cell transplantation in previous studies. Recent research shows that aspirin (ASP) has great potential in promoting bone regeneration. The objective of the present study was to incorporate PLGA into ß-TCP combined with a lower single-dose local administration of ASP to enhance its in vivo biodegradation and bone tissue growth. After the creation of a rodent critical-sized femoral metaphyseal bone defect, PLGA -modified ß-TCP (TP) was prepared by mixing sieved granules of ß-TCP and PLGA (50:50, v/v) for medical use, then TP with dripped 50 µg/0.1 ml and 100 µg/0.1 ml aspirin solution was implanted into the defect of OVX rats until death at 8 weeks. The defected area in distal femurs of rats was harvested for evaluation by histology, micro-CT, biomechanics and real time RT-PCR. The results of our study show that a single-dose local administration of ASP combined with the local usage of TP can increase the healing of defects in OVX rats. Single-dose local administration of aspirin can improve the transcription of genes involved in the regulation of bone formation and vascularization in the defect area, and inhibits osteoclast activity. Furthermore, treatments with a higher single-dose local administration of ASP and TP showed a stronger effect on accelerating the local bone formation than while using a lower dose of ASP. The results from our study demonstrate that the combination of a single-dose local administration of ASP and ß-TCP/PLGA had an additive effect on local bone formation in osteoporosis rats, and bone regeneration by PLGA/ß-TCP/ASP occured in a dose-dependent manner.

Prevention of ovariectomy-induced osteoporosis in rats : Comparative study of zoledronic acid, parathyroid hormone (1-34) and strontium ranelate.

Recently, the use of the pharmacological agents strontium ranelate (SR), parathyroid hormone (1-34, PTH) and zoledronic acid (ZA) has come to prominence for the treatment of osteoporosis due to their ability to prevent bone loss in osteoporotic patients. Although much emphasis has been placed on using pharmacological agents for the prevention of disease, much less attention has been placed on which one is more effective. There is still no direct comparative study on these three drugs. The aim of the present study was to investigate the effect of SR, PTH, ZA on preventing ovariectomy-induced osteoporosis in rats. After bilateral ovariectomy the rats randomly received vehicle, SR (500 mg/kg body weight/day, orally), PTH (20 µg/kg/day, subcutaneously) or a single injection of ZA (0.1 mg/kg, i.v.) until death at 12 weeks. The distal femurs were harvested for evaluation of bone metabolism. The rats treated with ZA demonstrated the highest levels of new bone formation as assessed by microcomputed tomography (CT), biomechanical strength, histological analysis and bone metabolism. Furthermore, PTH and SR showed a stronger effect on improving trabecular bone mass at 12 weeks. The results from the present study demonstrate that systemic administration of PTH, SR and ZA could prevent bone loss, while a single dose of ZA has a better effect on preventing ovariectomy-induced osteoporosis than either PTH or SR.