Odanacatib Inhibits Resistin-induced Hypertrophic H9c2 Cardiomyoblast Cells Through LKB1/AMPK Pathway

ABSTRACT Odanacatib (ODN) is a selective inhibitor of cathepsin K. The cysteine protease cathepsin K has been implicated in cardiac hypertrophy. Resistine is an adipokine which is identified to promote cardiac hypertrophy. Here, we hypothesize that ODN mitigates resistin-induced myocyte hypertrophy. Cell surface area and protein synthesis were measured after treatment with resistin and ODN in H9c2 cells. The expression of cardiomyocyte hypertrophy marker BNP and β-MHC was detected by RT-qPCR. The expression and phosphorylation of AMPK and LKB1 were analyzed with Western blot. Resistin could significantly increase cardiomyocyte cell surface area, protein synthesis, and embryonic gene BNP and β-MHC expression, inhibit phosphorylation of AMPK and LKB1. ODN could significantly reverse the effects of resistin. Collectively, our data suggest that ODN can inhibit cardiomyocyte hypertrophy induced by resistin and the underlying mechanism may be involved in LKB1/AMPK pathway.

Odanacatib inhibits relapse of orthodontic tooth movement: an in vivo micro-CT analysis / 安徽医科大学学报

To evaluated the inhibition effect of local injection of odanacatib on orthodontic relapse.Thirty rats were randomly divided into 2 groups(n =15).The maxillary right first molars of all animals were subjected to orthodontic force and moved mesially.Three weeks later,the force was removed,and the teeth relapsed.The rats of experimental group were received local injections of odanacatib.The control group received saline instead.Tooth movement and relapse were measured when appliances removed after 0 day and 2 weeks.The rats were sacrificed after the 2-week relapse.The microcomputed tomography analysis was performed to quantify the alveolar bone,and the values of bone mineral density(BMD) and bone volume fraction(BVF) were measured.The percentage of relapse in the experimental group was significantly lower than that in the control group(P ＜0.05),and the BMD and BVF of alveolar bone in the experimental group were significantly higher than those in the control group(P ＜0.05).Local injection of odanacatib effectively inhibit the relapse after orthodontic tooth movement in rats.

Progress in Cathepsin K Inhibitor Odanacatib / 天津医药

The prevalence of osteoporosis has increased during recent years. The activation in the function of osteo?clast is the main reason of osteoporosis. Cathepsin is expressed by osteoclast and involved in the degradation of collagen of bone,and causes osteoporosis. Cathepsin K is a kind of most important enzyme in the family of cathepsin. Odanacatib(ODN) is the inhibitor of cathepsin K, and it may be used to anti-osteoporosis thought inhibiting the degradation of bone collagen. It was found that the cortical thickness and bone minerals of cancellous increased after taking ODN in the studies, and then the density and the strength of bone increased. This study reviewed the pharmacological profile of ODN and the progresses of ani?mal study and clinical trials about ODN.