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

Abstract

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.

Silymarin from Milk Thistle Fruits Counteracts Selected Pathological Changes in the Lenses of Type 1 Diabetic Rats

“…Such differences in enzyme reaction can result from many factors, including the cellular context or reactive oxygen species concentration, to which a tissue or an organ is currently exposed [ 80 ]. A decreased activity of antioxidative enzymes during diabetes observed in the case of the serum is consistent with other studies performed on rat models [ 64 , 65 , 81 ] and in patients with type 1 diabetes [ 82 ]. Moreover, in the serum of the diabetic rats, an increased level of malondialdehyde, a marker of oxidative damage of lipids, was observed.…”

Ficus deltoidea promotes bone formation in streptozotocin-induced diabetic rats

“… 2019 ; Zheng et al. 2020 ). Intriguingly, STZ induces similar bone pathologies changes as seen in human T1DM (Motyl and McCabe 2009 ).…”

Role of osteogenic Dickkopf-1 in bone remodeling and bone healing in mice with type I diabetes mellitus

“…Our key finding revolves around the osteoblast-mediated inhibition of bone resorption in diabetic Cre+ mice, which seems to be the most essential contributor to bone protection. While various studies suggest low or normal bone resorption rates in individuals with T1DM 18,[41][42][43][44][45] , in the STZ mouse model, most studies report increased bone resorption rates [46][47][48][49] . Further, Coe et al showed attenuated bone loss in diabetic mice under alendronate treatment 50 .…”