Objectives: The current study aimed at determining the effects of degarelix on bone turnover, bone densitometry, and bone mechanical strength in male rats.
Methods: Eighteen male Sprague-Dawley rats were randomly divided into sham (SHAM), orchidectomized (ORX), and degarelix-induced (DGX) groups. Chemical castration was performed by subcutaneous degarelix injection (2 mg/kg) at the scapular region. The rats were scanned for baseline bone mineral area (BMA), bone mineral content (BMC), and bone mineral density (BMD) using dual-energy x-ray absorptiometry (DXA). Following six weeks of experimental period, BMA, BMC, and BMD were measured again with DXA and blood was collected for testosterone and bone biomarkers (osteocalcin and C-terminal of type I collagen crosslink (CTX-1)) measurements. The rats were euthanized and femora were dissected for bone biomechanical strength analysis.
Results: Bilateral orchidectomy and degarelix administration significantly lowered serum testosterone level, decreased whole body BMC, femoral BMA, femoral BMC, and femoral BMD (P < 0.05) compared with the SHAM group. However, no significant changes were observed in bone biochemical markers and bone mechanical strength in all experimental groups.
Conclusions: In conclusion, degarelix administration had comparable effects on bone as bilateral orchidectomy. Administration of degarelix provides an alternative method of inducing testosterone deficient-osteopenia in male rats without need for removing the testes.
Materials and Methods: Thirty-six female Sprague-Dawley rats were divided into six groups: Sham-operated (SHAM), OVX control, OVX and given Premarin at 64.5 µg/kg (OVX+E2), OVX and given VCO at 4.29 ml/kg (OVX+V), OVX and given TRF at 30 mg/kg (OVX+T), and OVX and given a combination of VCO at 4.29 ml/kg and TRF at 30 mg/kg (OVX+VT). Following 24 weeks of treatments, blood and femora samples were taken for analyses.
Results: There were no significant differences in serum osteocalcin levels between the groups (p>0.05), while serum C-terminal telopeptide of Type I collagen levels of the OVX+VT group were significantly lower than the other groups (p<0.05). The dynamic bone histomorphometry analysis of the femur showed that the double-labeled surface/bone surface (dLS/BS), mineral apposition rate, and bone formation rate/BS of the OVX+E2, OVX+T, and OVX+VT groups were significantly higher than the rest of the groups (p<0.05).
Conclusion: A combination of VCO and TRF has the potential as a therapeutic agent to restore bone loss induced by ovariectomy and high-fat diet.
METHODS: We established an in vitro OA culture model by exposing human chondrocytes to proinflammatory cytokine and interleukin (IL)-1β for 36 hours prior to treatment with the herbals: C. quadrangularis, W. somnifera, and the combination of the two herbals. Cell viability, toxicity, and gene expression of OA modifying agents were examined. In addition, expression of survivin, which is crucial for cell growth, was analyzed. In vivo work on osteotomized rats studied the bone and cartilage regenerative effects of C. quadrangularis, W. somnifera, and the combination therapy.
RESULTS: Exposure of chondrocytes to IL-1β induced significant toxicity and cell death. However, herbal treatment alleviated IL-1β induced cell toxicity and upregulated cell growth and proliferation. C. quadrangularis inhibited gene expression of cytokines and matrix metalloproteinases, known to aggravate cartilage and bone destruction, and augmented expression of survivin by inhibiting p38 MAPK. Interestingly, osteotomized rats treated with C. quadrangularis drastically enhanced alkaline phosphatase and cartilage tissue formation as compared to untreated, W. somnifera only, or the combination of both herbals.
CONCLUSION: Our findings demonstrate for the first time the signaling mechanisms regulated by C. quadrangularis and W. somnifera in OA and osteogenesis. We suggest that the chondroprotective effects and regenerative ability of these herbals are via the upregulation of survivin that exerts inhibitory effects on the p38 MAPK signaling pathway. These findings thus validate C. quadrangularis as a potential therapeutic for rheumatic disorders.