CYT387, a JAK-Specific Inhibitor Impedes Osteoclast Activity and Oophorectomy-Induced Osteoporosis via Modulating RANKL and ROS Signaling Pathways

• DOI: 10.3389/fphar.2022.829862
• Publication Date: 2022-03-08T05:55:57Z
• Authors: Jing Li; Jiamin Liang; Liwei Wu; Yang Xu; Chengxiang Xiao; Xue Yang; Ran Sun; Jinmin Zhao; Jiake Xu; Qian Liu; Bo Zhou
• Keywords: Pharmacology; ERK; 0303 health sciences; 03 medical and health sciences; CYT387; osteoclast; ROS; Therapeutics. Pharmacology; RM1-950; osteoporosis; 3. Good health

Osteoclasts are of hematopoietic lineage and have the ability to degrade mineralized bone tissues. Abnormalities in osteoclastic activity under certain pathological conditions common diseases such as osteoporosis, osteosclerosis, arthritis. Although many kinds drugs currently used treat they obvious adverse reactions limitations. CYT387 is a new small-molecule Janus kinase (JAK) inhibitor involved hematopoiesis, immune modulation, fertility, lactation, embryonic development. However, it has remained unclear whether functionally impacts osteoclast formation. Our study demonstrated through formation assay vitro, that use potential drug candidate for treating osteoclast-associated disease. The effects on formation, resorption, NFATc1 activation, especially intracellular ROS levels were investigated vitro. Further, we examined preclinical prospects using an oophorectomy (OVX) mouse model osteoporosis with its anti-osteoclast vivo. On whole, this shows holds promise osteoclast-related illnesses including osteoporosis.