Yubo Guo1, Lili Wang1, Rufeng Ma1, Qianqian Mu1, Na Yu1, Yi Zhang1, Yuqing Tang1, Yu Li1, Guangjian Jiang2, Dandan Zhao2, Fangfang Mo2, Sihua Gao3, Meijuan Yang1, Feifei Kan1, Qun Ma4, Min Fu5, Dongwei Zhang6. 1. Preclinical Medicine School, Beijing University of Chinese Medicine, Beijing 100029, China. 2. Diabetes Research Center, Beijing University of Chinese Medicine, Beijing 100029, China. 3. Diabetes Research Center, Beijing University of Chinese Medicine, Beijing 100029, China. Electronic address: gaosihua1216@163.com. 4. Chinese Material Medical School, Beijing University of Chinese Medicine, Beijing 100029, China. 5. McGill University Health Center, Montreal, Quebec H4A 3J1, Canada. 6. Diabetes Research Center, Beijing University of Chinese Medicine, Beijing 100029, China. Electronic address: dongwei1006@gmail.com.
Abstract
AIM: To assess the beneficial effects of JiangTang XiaoKe (JTXK) granule on the bone metabolism in high fat diet (HFD) fed KK-Ay diabetic mice. MATERIALS AND METHODS: The KK-Ay mice were used as a diabetic model, while C57BL/6 mice were utilized as the non-diabetic control. The left tibia was used for determining bone mineral density (BMD) and bone ash coefficient. The HE and alizarin red S staining of femur were employed to evaluate bone pathology and calcium deposition. The expressions of alkaline phosphatase (ALP), insulin growth factor 1 (IGF-1) and cathepsin K were assessed by western blotting and immunohistochemical staining. KEY FINDINGS: JTXK granule significantly improved the bone ash coefficient, the distribution of trabecular bone and the calcification nodules deposition in KK-Ay mice with diabetes. IGF-1 and ALP expressions were significantly decreased, and cathepsin K expression was dramatically increased in the HFD fed KK-Ay diabetic model mice, which can be reversed by JTXK granule treatment. JTXK granule at medium or high dosage was more efficient in improving diabetic bone quality when compared with that in mice with a low dosage. However, the BMD values in each group of KK-Ay diabetic mice were not significantly different. SIGNIFICANCE: We demonstrate that cathepsin K expression is increased in KK-Ay diabetic mouse model. JTXK granule treatment inhibits osteoclastic bone resorption and promotes the new bone formation by decreasing cathepsin K activity and increasing IGF-1 and ALP levels. These changes may contribute to the increase of bone strength and thus reducing the risk of bone fractures.
AIM: To assess the beneficial effects of JiangTang XiaoKe (JTXK) granule on the bone metabolism in high fat diet (HFD) fed KK-Ay diabeticmice. MATERIALS AND METHODS: The KK-Ay mice were used as a diabetic model, while C57BL/6 mice were utilized as the non-diabetic control. The left tibia was used for determining bone mineral density (BMD) and bone ash coefficient. The HE and alizarin red S staining of femur were employed to evaluate bone pathology and calcium deposition. The expressions of alkaline phosphatase (ALP), insulin growth factor 1 (IGF-1) and cathepsin K were assessed by western blotting and immunohistochemical staining. KEY FINDINGS: JTXK granule significantly improved the bone ash coefficient, the distribution of trabecular bone and the calcification nodules deposition in KK-Ay mice with diabetes. IGF-1 and ALP expressions were significantly decreased, and cathepsin K expression was dramatically increased in the HFD fed KK-Ay diabetic model mice, which can be reversed by JTXK granule treatment. JTXK granule at medium or high dosage was more efficient in improving diabetic bone quality when compared with that in mice with a low dosage. However, the BMD values in each group of KK-Ay diabeticmice were not significantly different. SIGNIFICANCE: We demonstrate that cathepsin K expression is increased in KK-Ay diabeticmouse model. JTXK granule treatment inhibits osteoclastic bone resorption and promotes the new bone formation by decreasing cathepsin K activity and increasing IGF-1 and ALP levels. These changes may contribute to the increase of bone strength and thus reducing the risk of bone fractures.
Authors: C Liu; L Wang; R Zhu; H Liu; R Ma; B Chen; L Li; Y Guo; Q Jia; S Shi; D Zhao; F Mo; B Zhao; J Niu; M Fu; A N Orekhov; D Brömme; S Gao; D Zhang Journal: Osteoporos Int Date: 2018-08-27 Impact factor: 4.507