title: JiangTang XiaoKe granule attenuates cathepsin K expression and improves IGF-1 expression in the bone of high fat diet induced KK-Ay diabetic mice.
abstract: OBJECTIVE
  To assess the beneficial effects of JiangTang XiaoKe (JTXK) granule on the bone metabolism in high fat diet (HFD) fed KK-Ay diabetic mice.
  
  
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Preclinical Medicine School, Beijing University of Chinese Medicine, Beijing 100029, China.
authors.forename: Yubo
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Preclinical Medicine School, Beijing University of Chinese Medicine, Beijing 100029, China.
authors.forename: Lili
authors.initials: L
authors.lastname: Wang
authors.affiliation: Preclinical Medicine School, Beijing University of Chinese Medicine, Beijing 100029, China.
authors.forename: Rufeng
authors.initials: R
authors.lastname: Ma
authors.affiliation: Preclinical Medicine School, Beijing University of Chinese Medicine, Beijing 100029, China.
authors.forename: Qianqian
authors.initials: Q
authors.lastname: Mu
authors.affiliation: Preclinical Medicine School, Beijing University of Chinese Medicine, Beijing 100029, China.
authors.forename: Na
authors.initials: N
authors.lastname: Yu
authors.affiliation: Preclinical Medicine School, Beijing University of Chinese Medicine, Beijing 100029, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Preclinical Medicine School, Beijing University of Chinese Medicine, Beijing 100029, China.
authors.forename: Yuqing
authors.initials: Y
authors.lastname: Tang
authors.affiliation: Preclinical Medicine School, Beijing University of Chinese Medicine, Beijing 100029, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Li
authors.affiliation: Diabetes Research Center, Beijing University of Chinese Medicine, Beijing 100029, China.
authors.forename: Guangjian
authors.initials: G
authors.lastname: Jiang
authors.affiliation: Diabetes Research Center, Beijing University of Chinese Medicine, Beijing 100029, China.
authors.forename: Dandan
authors.initials: D
authors.lastname: Zhao
authors.affiliation: Diabetes Research Center, Beijing University of Chinese Medicine, Beijing 100029, China.
authors.forename: Fangfang
authors.initials: F
authors.lastname: Mo
authors.affiliation: Diabetes Research Center, Beijing University of Chinese Medicine, Beijing 100029, China. Electronic address: gaosihua1216@163.com.
authors.forename: Sihua
authors.initials: S
authors.lastname: Gao
authors.affiliation: Preclinical Medicine School, Beijing University of Chinese Medicine, Beijing 100029, China.
authors.forename: Meijuan
authors.initials: M
authors.lastname: Yang
authors.affiliation: Preclinical Medicine School, Beijing University of Chinese Medicine, Beijing 100029, China.
authors.forename: Feifei
authors.initials: F
authors.lastname: Kan
authors.affiliation: Chinese Material Medical School, Beijing University of Chinese Medicine, Beijing 100029, China.
authors.forename: Qun
authors.initials: Q
authors.lastname: Ma
authors.affiliation: McGill University Health Center, Montreal, Quebec H4A 3J1, Canada.
authors.forename: Min
authors.initials: M
authors.lastname: Fu
authors.affiliation: Diabetes Research Center, Beijing University of Chinese Medicine, Beijing 100029, China. Electronic address: dongwei1006@gmail.com.
authors.forename: Dongwei
authors.initials: D
authors.lastname: Zhang
mesh_terms: D000818:Animals; D015519:Bone Density / Q000187:drug effects / Q000502:physiology*; D056657:Cathepsin K / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism*; D059305:Diet, High-Fat / Q000009:adverse effects*; D004365:Drugs, Chinese Herbal / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use; D005786:Gene Expression Regulation; D007334:Insulin-Like Growth Factor I / Q000096:biosynthesis*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL
chemical_list: D004365:Drugs, Chinese Herbal; C519530:insulin-like growth factor-1, mouse; D007334:Insulin-Like Growth Factor I; D056657:Cathepsin K; C534132:Ctsk protein, mouse
keywords: Alkaline phosphatase (ALP); Bone ash coefficient; Cathepsin K; Insulin growth factor-1 (IGF-1); JiangTangXiaoKe (JTXK); KK-Ay diabetic mice