Application of dusp6 inhibitor bci in the preparation of osteoporosis drugs

An osteoporosis and drug technology, applied in the field of medicine, can solve problems such as unclear role of osteoclast differentiation-related diseases

Active Publication Date: 2022-03-08
THE SECOND AFFILIATED HOSPITAL ARMY MEDICAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Current research on DUSP6 mainly focuses on the treatment of tumors and immunity, but its role in osteoclast differentiation-related diseases is still unclear

Method used

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  • Application of dusp6 inhibitor bci in the preparation of osteoporosis drugs
  • Application of dusp6 inhibitor bci in the preparation of osteoporosis drugs
  • Application of dusp6 inhibitor bci in the preparation of osteoporosis drugs

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Experimental program
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Effect test

Embodiment 1

[0029] Cell culture and osteoclast differentiation

[0030] Mouse macrophages RAW264.7 were derived from ATCC cell bank (Shanghai, China) and cultured in DMEM (10% fetal bovine serum and 1% P / S). Bone marrow mononuclear macrophages (BMMs) were isolated from mouse femur and tibia, and cultured in α-MEM (10% fetal bovine serum, 1% penicillin / streptomycin double antibody and 50ng / mL M-CSF) for 48 hours. All cells in 5% CO 2Incubate at 37°C. 5 h before osteoclast induction, DUSP6-specific small interfering RNA (siRNA) oligonucleotide (40 nM; 5'-CGAUGCUUACGACAUUGUUUAATTUUAACAAUGUCGUAAGCAUCGTT-3') (Shanghai Shengong) was transfected by Lipofectamine 3000 (Invitrogen). Both cell types were differentiated using M-CSF (50 ng / mL) and RANKL (100 ng / mL). The degree of osteoclast differentiation of RAW264.7 cells and BMMs was determined on the 3rd and 5th day of induction, respectively. MC3T3-E1 cells (pre-osteogenic cell line) were grown in α-MEM (10% fetal calf serum and 1% penicilli...

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Abstract

The invention discloses the use of DUSP6 inhibitor BCI in the manufacture of drugs for preventing and treating osteoporosis. Within the effective dose, BCI has no toxic effect on mononuclear macrophages and does not affect their cell cycle and apoptosis, and significantly inhibits the osteoclast induction of RAW264.7 cells and primary mouse mononuclear macrophages (BMMs) induced by RANKL Cell differentiation and maturation, effectively inhibiting the fusion and osteophagy ability of mature osteoclasts induced by RANKL, significantly reducing the expression of osteoclast differentiation-specific genes such as NFATc1 and c-Fos, and strongly inhibiting STAT3 in the process of osteoclast differentiation and NF‑κB‑NFATc1 signaling pathway, inhibiting the reduction of bone mineral density and other related bone parameters in the in vivo model of osteoporosis.

Description

technical field [0001] The invention belongs to the technical field of medicine, and specifically relates to the use of DUSP6 inhibitors, especially compound BCI, in the manufacture of drugs for preventing and treating osteoporosis. Background technique [0002] Osteoporosis has become an important health problem for people over 50 years old in my country, especially among middle-aged and elderly women. On October 19, 2018, the National Health and Medical Commission released the first epidemiological survey of osteoporosis in China, showing that more than half of women over 65 years old in my country suffer from osteoporosis; nearly half of people over 50 years old have low bone density. The amount and density of osteoporosis are high-risk groups for osteoporosis, but the residents' awareness of osteoporosis is generally insufficient. Osteoporosis is the most common skeletal disease that affects the health of residents. There are usually no obvious clinical manifestations in...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K31/137A61P19/10
CPCA61K31/137A61P19/10
Inventor 蔡晨晖初同伟胡文辉张莹胡旭杨思振
Owner THE SECOND AFFILIATED HOSPITAL ARMY MEDICAL UNIV
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