1-MON for treating osteoarthritis and promoting cartilage repair

Abstract

The invention discloses an effect of 1-MON on treating osteoarthritis by targeting AKAP8L, and relates to the field of biological medicines. According to the application, 1-MON is injected into an articular cavity to treat a mouse OA model, the direct curative effect of 1-MON on OA is systematically evaluated from multiple aspects of cartilage synthesis catabolism, cartilage cell activity and the like, and in combination with a drug affinity response target stability experiment, immunoblotting verifies that AKAP8L plays a role as a target of 1-MON in osteoarthritis. According to the invention, 1-MON regulates chondrocyte metabolism by targeting AKAP8L, cartilage tissues are repaired, and osteoarthritis is delayed and treated.

Description

Technical Field

[0001] The present invention belongs to the field of biomedicine and relates to a new use of the small molecule compound 1-Monomyristin for delaying and treating osteoarthritis. Background Art

[0002] Osteoarthritis (OA) is a degenerative disease characterized by damage and degeneration of joint cartilage caused by factors such as strain, trauma, obesity, inflammation, aging, metabolic disorders, and genetics. In people over 50, OA can lead to long-term disability and an eventual mortality rate of up to 53%. Due to its extremely high disability and mortality rates, OA has become a leading cause of functional loss and disability in the elderly and a serious challenge to future public health.

[0003] Pathological studies have shown that the primary pathological changes of osteoarthritis (OA) include damage to articular cartilage, abnormal bone proliferation, and synovial hypertrophy. Studies have shown that due to the lack of vascular and nerve supply to cartilage, its self-repair capacity is extremely limited. As cartilage is damaged and degenerated, it gradually leads to tissue loss and dysfunction, ultimately causing progressive osteoarticular disease. Therefore, repairing articular cartilage damage and promoting cartilage regeneration are key challenges and challenges in current OA treatment, and are currently a key scientific issue being addressed in this research field.

[0004] Normal articular cartilage is hyaline cartilage composed of chondrocytes, cartilage matrix, and fibers. Its surface is smooth and elastic, and it can effectively absorb and buffer stress. Chondrocytes are the only cells in cartilage and are dispersed throughout the cartilage matrix. They maintain the balance of matrix components by participating in the decomposition and metabolism of the cartilage matrix. Various osteoarthritis related to articular cartilage damage and degeneration exhibit different self-repair capabilities depending on the degree of cartilage damage. Unlike normal hyaline cartilage, the repaired fibrocartilage cannot be tightly integrated with the surrounding tissue and gradually degenerates and disintegrates over time. Therefore, the regeneration and repair of hyaline cartilage is an urgent problem that needs to be solved. Summary of the Invention

[0005] This invention provides a small molecule compound for the treatment of osteoarthritis, namely 1-Monomyristin (1-MON). Its therapeutic efficacy against osteoarthritis (OA) has been demonstrated in a mouse osteoarthritis DMM (destabilization of the medial meniscus) model, as well as in human chondrocytes (C28I2) and primary chondrocytes. Studies have shown that 1-MON significantly promotes chondrocyte anabolism and growth and proliferation, while inhibiting chondrocyte apoptosis. Furthermore, 1-MON also slows OA-induced cartilage degradation in the DMM mouse model, demonstrating that 1-MON can slow the progression of osteoarthritis and achieve its therapeutic effect by delaying articular cartilage degeneration and chronic synovial inflammation in OA.

[0006] In addition, AKAP8L was isolated as a new target of 1-MON in regulating chondrocytes, and 1-MON achieves its therapeutic effect on OA by targeting AKAP8L.

[0007] The present invention discovers and proves that the small molecule compound 1-MON has obvious biological effects of promoting cartilage regeneration and repair and delaying cartilage damage.

[0008] The molecular formula of 1-MON is C17H34O4; the molecular weight is 302.45; its molecular structure is shown in Figure 1 . BRIEF DESCRIPTION OF THE DRAWINGS

[0009] In order to more clearly illustrate the content of the present invention, the following briefly introduces the drawings required for use.

[0010] Figure 1 It is the structural formula of 1-MON.

[0011] Figure 2 The effect of different concentrations of 1-MON on chondrocyte viability when treated with the inflammatory factor IL-1β.

[0012] Figure 3 The following are the results of HE, safranin fast green and toluidine blue staining of articular cartilage tissue in mice 6 weeks after intra-articular injection of 1-MON, as well as the OARSI score, cartilage thickness and chondrocyte quantitative analysis of articular cartilage.

[0013] Figure 4 Six weeks after intra-articular injection of 1-MON in mice, immunohistochemical staining was used to analyze the localization and expression of SOX9 and COL2, marker genes for anabolic metabolism in articular cartilage tissue.

[0014] Figure 5 Six weeks after the mice were injected with 1-MON into the joint cavity, immunohistochemical staining was used to analyze the localization and expression of MMP13 and ADAMTS7, marker genes for decomposition of articular cartilage tissue.

Claims

1. Use of a new small molecule natural drug 1-MON in the treatment of osteoarthritis.

2. The use according to claim 1, characterized in that: Injection into the joint cavity can repair cartilage, delay cartilage damage, and achieve a therapeutic effect on OA.

3. This invention belongs to the field of medicine and health and can be directly applied to clinical and basic medical fields such as orthopedic surgery or trauma repair.

4. Use of the small molecule natural medicine according to claim 1 in preparing medicines for treating osteoarthritis and other related diseases.

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