CN-121987791-A - Application of LRP1 in preparation of osteoarthritis medicines

Abstract

The invention discloses an application of LRP1 in preparation of osteoarthritis medicines, and belongs to the technical field of biological medicines. The m 6 A methylase can mediate lipid metabolism reprogramming through LRP1, regulate and control the immune homeostasis of macrophages, regulate the chondrogenic differentiation of bone marrow mesenchymal stem cells, further promote the repair and regeneration of articular cartilage, and provide a potential novel double-regulation and control strategy of immune metabolism for the treatment of osteoarthritis patients.

Inventors

• HUANG CHENYAN
• WEI YAN
• YANG YUE
• GAO ZHENGRONG
• CHEN CHEN

Assignees

• 北京大学口腔医学院
• 南京市口腔医院

Dates

Publication Date

20260508

Application Date

20260129

Claims (9)

1. The application of LRP1 as a molecular target in preparing an osteoarthritis prevention or treatment drug.
2. Application of LRP1 as molecular target in preparing medicine for promoting cartilage repair and regeneration.
3. 3. The use according to claim 1 or 2, wherein LRP1 is involved in regulating lipid metabolism reprogramming and maintaining regenerative microenvironment homeostasis via Wnt signaling pathway or autophagy, playing a target role in WTAP-mediated m 6 a-related cartilage regeneration process.
4. 4. The use according to claim 1 or 2, wherein the wilms tumor 1 associated protein WTAP mediates m 6 a to regulate macrophage anti-inflammatory polarization through LRP 1-lipid metabolism axis, promote bone marrow mesenchymal stem cell chondrogenic differentiation, and participate in regulating OA cartilage injury repair.
5. 5. A prophylactic or therapeutic agent for osteoarthritis, which is highly bound to LRP1 and activates a relevant lipid metabolism pathway.
6. 6. The osteoarthritis prevention or treatment drug of claim 5, wherein the drug comprises at least one of silymarin and estradiol benzoate.
7. 7. The application of silymarin in preparing medicaments for repairing OA cartilage injury is characterized in that the medicaments take LRP1 as a targeting site, and the LRP 1-lipid metabolism axis is regulated and controlled by combining with the LRP1, so that the anti-inflammatory polarization of macrophages and the promotion effect of chondrogenic differentiation of bone marrow mesenchymal stem cells are realized.
8. 8. The application of the estradiol benzoate in preparing a medicament for repairing OA cartilage injury is characterized in that the medicament takes LRP1 as a targeting site, and the LRP 1-lipid metabolism axis is regulated and controlled by combining with the LRP1, so that the anti-inflammatory polarization of macrophages and the promotion effect of chondrogenic differentiation of bone marrow mesenchymal stem cells are realized.
9. The application of LRP1 as a target in screening medicines for repairing OA cartilage injury is characterized in that a small molecular compound highly combined with LRP1 is screened by a molecular docking technology, and the small molecular compound can promote OA cartilage injury repair by regulating an LRP 1-lipid metabolism axis.

Description

Application of LRP1 in preparation of osteoarthritis medicines Technical Field The invention belongs to the technical field of biomedical technology, and particularly relates to a method for identifying osteoarthritis treatment targets and screening medicines. Background Osteoarthritis (Osteoarthritis, OA) is a refractory chronic disease characterized by injury to articular cartilage as the primary pathological feature. The incidence of OA continues to rise as the global population ages and the proportion of obese people increases. Because of the characteristics of the articular cartilage such as no blood vessel, nerve and lymphatic tissue, once the injury is hard to repair by itself. The modes of treating cartilage injury commonly used clinically at present mainly comprise intra-articular cavity medicine injection and surgical operation treatment. The intra-articular medicine injection has the advantages of being minimally invasive, easy to operate and the like, can play roles in relieving pain and slowing down the development process of diseases, but cannot realize cartilage regeneration, and the surgical treatment can realize cartilage regeneration to a certain extent, but has larger wounds, does not accord with the principle of minimally invasive treatment, and the prognosis is closely related to the individual recovery condition. Therefore, the research of a minimally invasive and efficient cartilage regeneration treatment strategy has important significance for clinical treatment of OA. Recent studies have shown that epigenetic mechanisms play an important regulatory role in tissue regeneration. Among them, N6-methyladenine (m 6 A), one of the most common RNA epigenetic modifications, has been demonstrated to be widely involved in disease progression and regulation of tissue regeneration. In cartilage biology, m 6 a can significantly influence the proliferation, migration and differentiation processes of chondrocytes. At the same time, m 6 A is also deeply involved in cell metabolism regulation, especially plays a key role in lipid metabolism. Metabolic reprogramming is not only the basis for maintenance of immune microenvironment homeostasis, but also the central link in regulating cell differentiation, and lipid metabolism abnormalities are of great importance in the development and progression of Osteoarthritis (OA). As a key receptor family in lipid metabolism, the low density lipoprotein receptor-related protein (LRP) family plays an important role in the metabolic reprogramming process associated with tissue regeneration. However, the specific mechanism of action of m 6 a in cartilage regeneration through lipid metabolism reprogramming is not yet known. Therefore, the immune metabolism regulation mechanism of OA epigenetic is deeply explored, and a drug treatment strategy taking the immune metabolism regulation mechanism as a target point is developed, so that the immune metabolism regulation mechanism has important clinical value and application prospect. Disclosure of Invention The invention aims to provide an application of LRP1 in preparation of osteoarthritis drugs and a drug screening method based on the target point, and aims to provide a novel potential epigenetic immune metabolism regulation strategy for treatment of osteoarthritis patients. The invention discovers that the kidney cytoma 1 related protein (WTAP) mediates m 6 A to regulate and control macrophage anti-inflammatory polarization through LRP 1-lipid metabolism axis, promote bone marrow mesenchymal stem cell chondrogenic differentiation and participate in regulating and controlling OA cartilage injury repair. The invention further screens out small molecular drugs silymarin (Silibinin) and estradiol benzoate (Estradiol Benzoate) which are highly combined with LRP1 through molecular docking targeting drugs, thereby providing a new strategy for OA minimally invasive targeting drug treatment. The CAS number of silymarin is 65666-07-1, and the structural formula is shown as follows: 。 the CAS number of the estradiol benzoate is 50-50-0, and the structural formula is shown as follows: 。 the technical scheme of the invention is as follows: In a first aspect of the invention, a target for osteoarthritis treatment is provided. The application of LRP1 as a molecular target in preparing an osteoarthritis prevention or treatment medicament. The invention mainly focuses on the regulation and control relation between the epigenetic level m 6 A modification and the LRP1 mediated lipid metabolism pathway, so as to promote and regulate the mechanism of OA cartilage regeneration, and the core mechanism is a regulation and control axis of 'WTAP-LRP 1-lipid metabolism-cartilage regeneration'. Studies of the invention show that WTAP mediated m 6 A modification is an epigenetic regulator of cartilage regeneration at the cellular level and the animal level, WTAP is a key subunit of m 6 A methylase METTL3/METTL14 complex, is mainly responsible for