Lycopene ameliorates diabetic osteoporosis via anti-inflammatory, anti-oxidation, and increasing Osteoprotegerin/RANKL expression ratio

Aims: This research aimed at exploring potential new compound in the treatment of osteoporosis by Connectivity Map (CMap) and determining the role of fisetin on osteoporosis according to its effects on PI3K-AKT signaling pathway in MC3T3-E1 pre-osteoblastic cells. Methods: Microarray analysis was used to obtain the differentially expressed genes in published gene expression data. Potent compounds for osteoporosis therapy were discovered by CMap analysis. DAVID and gene set enrichment analysis (GSEA) were used to discover signaling pathways that connected to osteoporosis disease. Cell viability was evaluated by a CCK-8 assay. Quantitative real-time polymerase chain reaction (qRT-PCR) and western blot analysis were used to test the mRNA and protein expressions related to PI3K-AKT signaling pathway in MC3T3-E1 cells respectively. Results: CMap analysis identified fisetin as a promising compound for anti-osteoporosis treatment. DAVID and GSEA analysis showed that the PI3K-AKT signaling pathway was inactivated in osteoporosis. Cell experiments revealed that fisetin caused an elevation of cell viability, up-regulated the mRNA levels of the runt-related transcription factor-2 (Runx2), osterix (Osx), collagen type I 1 (Col1a1) and osteoprotegerin (OPG) while down-regulated the nuclear factor-κB ligand (RANKL) mRNA level. Discussion: The protein levels of Runx2, Col1a1 and osteocalcin(OCN) were also increased by fisetin. Furthermore, fisetin activated the phosphoinositide-3-kinase/protein kinase B (PI3K-AKT) signaling pathway, and blocking this pathway by the inhibitor LY-294002 could impair fisetin’s functions on proliferation, differentiation and OPG/RANKL expression ratio in the MC3T3-E1 cells. Conclusion: Our results demonstrated that fisetin could promote MC3T3-E1 cell proliferation, differentiation, and increase OPG/RANKL expression ratio through activating the PI3K-AKT pathway, which has potential in the treatment of osteoporosis.

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The Anti-Inflammatory, Phytoestrogenic, and Antioxidative Role ofLabisia pumilain Prevention of Postmenopausal Osteoporosis

Advances in Pharmacological Sciences ◽

10.1155/2012/706905 ◽

2012 ◽

Vol 2012 ◽

pp. 1-7 ◽

Cited By ~ 6

Author(s):

M. E. Nadia ◽

A. S. Nazrun ◽

M. Norazlina ◽

N. M. Isa ◽

M. Norliza ◽

...

Keyword(s):

Free Radical Scavenger ◽

Radical Scavenger ◽

Low Bone Mass ◽

Rankl Expression ◽

Effective Agent ◽

Women Studies ◽

Positive Effects ◽

Tnf Α ◽

Anti Inflammatory ◽

Inflammatory Effect

Osteoporosis is characterized by skeletal degeneration with low bone mass and destruction of microarchitecture of bone tissue which is attributed to various factors including inflammation. Women are more likely to develop osteoporosis than men due to reduction in estrogen during menopause which leads to decline in bone-formation and increase in bone-resorption activity. Estrogen is able to suppress production of proinflammatory cytokines such as IL-1, IL-6, IL-7, and TNF-α. This is why these cytokines are elevated in postmenopausal women. Studies have shown that estrogen reduction is able to stimulate focal inflammation in bone.Labisia pumila(LP) which is known to exert phytoestrogenic effect can be used as an alternative to ERT which can produce positive effects on bone without causing side effects. LP contains antioxidant as well as exerting anti-inflammatory effect which can act as free radical scavenger, thus inhibiting TNF-α production and COX-2 expression which leads to decline in RANKL expression, resulting in reduction in osteoclast activity which consequently reduces bone loss. Hence, it is the phytoestrogenic, anti-inflammatory, and antioxidative properties that make LP an effective agent against osteoporosis.

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Chondroitin Sulfate Prevents STZ Induced Diabetic Osteoporosis through Decreasing Blood Glucose, AntiOxidative Stress, Anti-Inflammation and OPG/RANKL Expression Regulation

International Journal of Molecular Sciences ◽

10.3390/ijms21155303 ◽

2020 ◽

Vol 21 (15) ◽

pp. 5303 ◽

Cited By ~ 2

Author(s):

Hong Xing Zheng ◽

De Jing Chen ◽

Yue Xin Zu ◽

En Zhu Wang ◽

Shan Shan Qi

Keyword(s):

Blood Glucose ◽

Chondroitin Sulfate ◽

Treated Group ◽

Diabetic Rats ◽

Diabetic Rat ◽

Rankl Expression ◽

Mineral Density ◽

Diabetic Osteoporosis ◽

Antioxidative Stress ◽

Anti Inflammation

Chondroitin sulfate (CS) has antioxidative, anti-inflammatory, anti-osteoarthritic and hypoglycemic effects. However, whether it has antidiabetic osteoporosis effects has not been reported. Therefore, in this study, we established a STZ-induced diabetic rat model; CS (500 mg kg−1 d−1) was orally administrated for eight weeks to study its preventive effects on diabetic osteoporosis. The results showed that eight weeks of CS treatment improved the symptoms of diabetes; the CS-treated group has increased body weight, decreased water or food intake, decreased blood glucose, increased bone-mineral density, repaired bone morphology and decreased femoral osteoclasts and tibia adipocytes numbers. After CS treatment, bone histomorphometric parameters returned to normal, the levels of serum inflammatory cytokines (IL-1β, IL-6 and TNF-α) decreased significantly, serum SOD, GPX and CAT activities increased and MDA level increased. In the CS-treated group, the levels of serum ALP, CTX-1, TRACP 5b, osteocalcin and RANKL decreased and the serum RUNX 2 and OPG levels increased. Bone immunohistochemistry results showed that CS can effectively increase the expression of OPG and RUNX2 and reduce the expression of RANKL in diabetic rats. All of these indicate that CS could prevent STZ induced diabetic osteoporosis—mainly through decreasing blood glucose, antioxidative stress, anti-inflammation and regulation of OPG/RANKL expression. CS can therefore effectively prevent bone loss caused by diabetes.

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