Abstract

Diabetic Osteoporosis (DOP) is a common metabolic bone disease, characterized by decreased bone mineral density (BMD) and destruction of bone microstructure. It has been reported that icariin is beneficial for estrogen deficiency-induced osteoporosis, and alcohol-induced osteoporosis; whether icariin has protective effects on diabetes-induced osteoporosis has not been reported. In this study, a rat model of diabetic osteoporosis was established by streptozotocin injection, the bone protective effects and potential mechanism of icariin on diabetes-induced bone loss was observed. Thirty 8-week-old female Sprague Dawley rats were divided into control group (vehicle treatment), T1DM (diabetic) group and T1DM-icariin (ICA) group (diabetic rats treated with icariin), 10 rats in each group. The bone histomorphometry parameters, bone mineral density (BMD), serum bone turnover markers, and bone marrow adipogenesis were analyzed after 8 weeks of icariin administration. The results showed consumption of icariin at a doses of 100 mg kg−1 decreased blood glucose, and increased the BMD of diabetic rats. Icariin effectively decreased serum bone turnover marker levels, including CTX-1, ALP, TRACP 5b, osteocalcin, and PINP. Meanwhile, the bone histomorphometry parameters, the number of osteoclasts per bone perimeter were turned to be normal level, and the icariin treatment suppressed bone marrow adipogenesis. The runt-related transcription factor 2 (RUNX 2), as well as the osteoprotegerin (OPG)/receptor activator of nuclear factor-κ B ligand (RANKL) ratio in serum and bone tissues were increased significantly after icariin treatment in diabetic rats. All of the above indicate that oral administration of icariin can prevent diabetic osteoporosis; the effect is mainly related to its ability to reduce blood glucose, inhibit bone turnover and bone marrow adipogenesis, as well as up-regulate bone RUNX 2, and OPG expression.

Highlights

  • With the improvement of people’s living standards and changes in eating habit, the number of diabetic patients has been increasing

  • Bone mineral density analysis results showed that the lumbar (L1–L4) and femoral bone mineral density (BMD) were decreased in diabetic rats (p < 0.05), which were recovered by ICA treatment

  • These results suggest that ICA can increase BMD in diabetic rats

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Summary

Introduction

With the improvement of people’s living standards and changes in eating habit, the number of diabetic patients has been increasing. The use of postmenopausal requires long-term treatment boneAlthough resorptioninsulin inhibitors and bone formation bisphosphonates or raloxifene to has hypoglycemic effect, itpromoters, can inhibitsuch boneas turnover; hormone therapy has side treat DOP having adverse effects such and as constipation and gastrointestinal effects suchare as costly breast and cancer, hypoglycemia, headache flu-like symptoms [7,8,9]. Inhibit adipocyte differentiation and improve insulin, blood glucose and lipid metabolism in it was reported that icariin has anti-diabetic effects, can inhibit adipocyte differentiation and improve diabetic blood mice, glucose and improve diabetic complications such mice, as retinopathy, and diabetic cognitive deficits [17–.

Results
ICA Decreased Blood Glucose and Serum Bone Turnover Markers
ICA Increased
Effects of ICA on Bone Morphology and Bone Histomorphometry Parameters
ICA Decreased Bone Marrow Adipocyte Density and Adipocyte Diameter
Discussion
Animals
Establishment of Rat Model of Diabetes and ICA Administration
Bone Histomorphometric Analysis
Bone Marrow Adipocyte Parameters Analysis
Immunohistochemistry
Quantitative Real-Time PCR
Conclusions
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