CN-121971624-A - Application of MYC mRNA translation inhibitor in preparation of medicine for preventing and/or treating osteoarthritis

Abstract

The invention belongs to the technical field of biological medicines, and particularly relates to application of MYC mRNA translation inhibitor in preparation of a medicine for preventing and/or treating osteoarthritis. The MYC mRNA translation inhibitor is selected from biological materials capable of inhibiting or blocking MYC mRNA translation processes, decreasing MYC protein synthesis efficiency, or interfering with MYC mRNA steady-state levels. The invention provides a novel molecular target spot which can be used for treating osteoarthritis and a drug application scheme thereof.

Inventors

• ZHENG GUIHAO
• SUN GUICAI

Assignees

• 南昌大学

Dates

Publication Date

20260505

Application Date

20260306

Claims (10)

1. Use of an inhibitor of myc mRNA translation in the manufacture of a medicament for the prevention and/or treatment of osteoarthritis.
2. 2. The use of claim 1, wherein the MYC mRNA translational inhibitor is selected from biological materials capable of inhibiting MYC mRNA translation processes, decreasing MYC protein synthesis efficiency, or interfering with MYC mRNA steady state levels.
3. 3. The use of claim 1, wherein the MYC mRNA translational inhibitor is selected from any one of the following: b1 siRNA, the nucleotide sequence of the sense strand of the siRNA is shown as SEQ ID NO.1, and the nucleotide sequence of the antisense strand is shown as SEQ ID NO. 2; b2 shRNA, the nucleotide sequence of the sense strand of the shRNA is shown as SEQ ID NO.3, and the nucleotide sequence of the antisense strand is shown as SEQ ID NO. 4; B3 An eIF4F inhibitor selected from any one of the following: a) An eIF4A targeted inhibitor; b) An eIF4E/eIF4G interaction inhibitor; c) eIF4E targeted inhibitors; d) Inhibitors of the PI3K/Akt pathway.
4. 4. The use according to claim 1, wherein the pharmaceutical dosage form is selected from any one of injection, sustained release formulation, nano-formulation.
5. 5. The use according to claim 1, wherein the medicament further comprises a pharmaceutically acceptable carrier selected from one or more of physiological saline, phosphate buffer, biodegradable polymers, liposomes.
6. 6. The use according to claim 1, wherein the medicament is administered by intra-articular injection or systemically.
7. 7. The use of claim 6, wherein the MYC mRNA translational inhibitor is administered in a single dose of 0.01mg to 10mg when the medicament is administered by intra-articular cavity injection.
8. 8. The use according to claim 1, wherein the medicament further comprises a second active ingredient for the prevention and/or treatment of osteoarthritis, said second active ingredient being selected from any one of a non-steroidal anti-inflammatory drug, a glucocorticoid, a chondroprotective agent.
9. 9. The use according to claim 1, wherein the medicament is for inhibiting articular cartilage cell apoptosis, promoting cartilage matrix synthesis, alleviating articular cartilage damage or delaying osteoarthritic cartilage degeneration.
10. 10. The use of claim 1, wherein the medicament down-regulates MYC protein expression by inhibiting the translation process of MYC mRNA in a target cell selected from one or more of chondrocytes, synovial fibroblasts, synovial macrophages.

Description

Application of MYC mRNA translation inhibitor in preparation of medicine for preventing and/or treating osteoarthritis Technical Field The invention relates to the technical field of biological medicines, in particular to application of MYC mRNA translation inhibitor in preparation of a medicine for preventing and/or treating osteoarthritis. Background Osteoarthritis (Osteoarthritis, OA) is a chronic degenerative disease characterized by progressive degeneration of articular cartilage, the major pathological changes of which include degradation of the cartilage matrix, disorder of the chondrocyte phenotype, enhancement of synovial inflammatory response, and abnormal remodeling of subchondral bone. With the acceleration of the aging process of population, the incidence of osteoarthritis increases year by year, and the osteoarthritis becomes one of common chronic diseases which seriously affect the quality of life of middle-aged and elderly people and cause huge socioeconomic burden. At present, the clinical treatment of osteoarthritis is mainly symptomatic relief and mainly comprises non-steroidal anti-inflammatory drugs, joint cavity injection of glucocorticoid or hyaluronic acid, end-stage artificial joint replacement and the like. Although these treatments can relieve pain and improve joint function to some extent, they cannot interfere with the underlying pathological process of cartilage degeneration from a molecular level, and it is also difficult to block the continued progression of the disease. Therefore, finding new molecular targets and developing targeted therapeutic strategies with clear mechanisms of action is an important issue to be addressed in the basic research and clinical transformation fields of osteoarthritis. MYC (myelocytomatosis viral oncogene homolog, a cancer gene homolog of myeloblastosis virus) is taken as a core transcription factor, is widely involved in key biological processes such as cell proliferation, metabolic reprogramming, inflammatory reaction, cell steady state maintenance and the like, and has been studied to suggest that MYC plays an abnormal regulation role in various degenerative and inflammatory related diseases and is closely related to articular cartilage degeneration, synovial inflammation and cell aging. Meanwhile, the PI3K/AKT signal pathway is taken as a classical inflammatory response, cell survival and metabolism regulation pathway, and a plurality of researches prove that abnormal activation plays a key driving role in the occurrence and development of OA, and can promote cartilage degradation, inflammatory factor release and synovial hyperplasia and accelerate joint structural damage. However, there is no systematic study of MYC involved in the pathological course of osteoarthritis by modulating PI3K/AKT signaling pathway, and the specific biological functions, upstream and downstream regulatory networks and molecular mechanisms of MYC in the osteoarthritis joint microenvironment are still unknown. More importantly, no mature technical scheme or related patent report for preparing osteoarthritis treatment drugs by targeting MYC-PI3K/AKT axis by taking MYC as a direct intervention target is known. Therefore, there is a need to elucidate the role of MYC in osteoarthritis from a molecular mechanism and transformation application layer system, to clarify the control mechanism of MYC on PI3K/AKT pathway, to explore the feasibility and application value of MYC as a potential therapeutic target for osteoarthritis, and to provide theoretical basis and technical support for developing novel targeted therapeutic drugs. Disclosure of Invention In order to solve the problem that the existing osteoarthritis treatment means mainly stay in symptomatic relief and lack of definite molecular targeting intervention strategies, the invention provides application of MYC mRNA translation inhibitor in preparation of medicines for preventing and/or treating osteoarthritis. The MYC mRNA translation inhibitor is selected from biological materials capable of inhibiting or blocking MYC mRNA translation process, reducing MYC protein synthesis efficiency or interfering with MYC mRNA steady-state level, and helps to delay the progression of osteoarthritis. To achieve the above object, in one aspect, the present invention provides the use of MYC mRNA translational inhibitor for the preparation of a medicament for preventing and/or treating osteoarthritis. Preferably, the MYC mRNA translation inhibitor is selected from biological materials capable of inhibiting MYC mRNA translation processes, decreasing MYC protein synthesis efficiency, or interfering with MYC mRNA steady-state levels. Preferably, the MYC mRNA translation inhibitor is selected from any one of the following: b1 siRNA, the nucleotide sequence of the sense strand of the siRNA is shown as SEQ ID NO.1, and the nucleotide sequence of the antisense strand is shown as SEQ ID NO. 2; b2 shRNA, the nucleotide sequence of the sen