CN-122005757-A - Application of tectoridin in anti-yellow ligament ossification

Abstract

The invention provides an application of irisin in anti-ligamentum flavum ossification, in particular to an application of irisin, or a prodrug thereof, or a degradation product thereof, or a fusion protein thereof, wherein the irisin, or the prodrug thereof, or the degradation product thereof, or the fusion protein thereof is used for preparing a pharmaceutical composition, and the pharmaceutical composition is used for preventing and/or treating ligamentum flavum Ossification (OLF).

Inventors

• CHEN KAIWEN
• ZHENG CHAOJUN
• NIE CONG
• GU SHENYAN
• JI YUHANG
• JIANG JIANYUAN

Assignees

• 复旦大学附属华山医院

Dates

Publication Date

20260512

Application Date

20251204

Claims (10)

1. 1. The use of irisin, or a prodrug thereof, or a degradation product thereof, or a fusion protein thereof, for the preparation of a pharmaceutical composition for the prevention and/or treatment of yellow ligament ossification.
2. 2. The use according to claim 1, wherein the yellow ligament ossification is a mechanically stimulated yellow ligament ossification.
3. 3. The use according to claim 1, wherein the pharmaceutical composition is further for modulating calcium signaling.
4. 4. The use according to claim 1, wherein the pharmaceutical composition is further used for reducing intracellular ROS levels and/or reducing cellular oxidative stress.
5. 5. The use according to claim 1, wherein the pharmaceutical composition is further used for protecting mitochondrial homeostasis.
6. 6. The use of claim 1, wherein the pharmaceutical composition is further for down-regulating expression of an osteogenic-related marker in mammalian ligamentum flavum cells.
7. 7. The use according to claim 1, wherein the pharmaceutical composition is further for inhibiting osteogenic differentiation of a yellow ligament cell.
8. 8. The use of claim 7, wherein the osteogenic differentiation of the flavocytic cells is to the osteogenic differentiation of the flavocytic cells caused by the activation of the Piezo1 channel.
9. 9. The use according to claim 1, wherein the pharmaceutical composition is further for inhibiting the osteogenic differentiation of the yellow ligament cells caused by mechanical stimulation.
10. 10. A method for preventing and/or treating yellow ligament ossification, which comprises the step of administering a safe and effective amount of irisin, or a prodrug thereof, or a degradation product thereof, or a fusion protein thereof to a subject in need thereof.

Description

Application of tectoridin in anti-yellow ligament ossification Technical Field The invention relates to the fields of life science and medical technology, in particular to application of tectoridin in anti-yellow ligament ossification. Background Irisin (Irisin) is a myogenic factor secreted by skeletal muscle during exercise, and is a polypeptide fragment that is cleaved from fibronectin type III domain protein5 (fibronectin type III domain-containing protein5, FNDC 5), in a form that can enter the blood or be secreted by the side, to effect interactions [1-3] of muscle and other system structures of the body. As an endogenous substance which is produced by exercise and can spread throughout the whole body through various routes, irisin has been reported to play an important role in neurodegenerative diseases in various systems such as nervous system, endocrine system, skeletal system and cardiovascular system, by modulating inflammation, inhibiting iron death, activating autophagy and the like, alleviating disease progression and promoting tissue repair [4-8]. Yellow ligament ossification (ossification of ligamentum flavum, OLF) is a special disease [9-12] characterized mainly by abnormal ossification of the spinal yellow ligament. OLF is hidden, the incidence rate of people is about 3.6-36%, people who are good for middle-aged and elderly Asian people, and the incidence rate between sexes is not obviously different [9,12-17]. Although OLF can occur in any portion of the spine where ligamentum flavum is present, thoracic vertebrae are particularly common, and one of the main causes of stenosis in the thoracic spine. Importantly, the ossified ligamentum flavum often presses against the spinal cord, resulting in severe spinal cord injury, leading to paralysis and dysuria [18-19] in the patient. OLF is continuously aggravated as the course of the disease progresses, and there is currently no effective conservative treatment. Thus, surgical treatment is currently the most effective treatment for patients with symptomatic spine OLF. For the surgical treatment of the yellow ligament ossification, the yellow ligament ossification is well generated at the thoracic vertebrae, but because the thoracic medullary blood supply is poor, the ectopic ossification is often adhered to surrounding tissues (such as dura mater sac), so that the literature proves that the operation of the OLF is easy to cause operation related complications such as dural fluid leakage, postoperative infection and the like, about 10-20% of patients can also cause transient and even permanent exercise and abnormal sensory functions to aggravate after the operation due to ischemia reperfusion injury [9] and the like, thereby causing serious injury to the body and mind of the patients, and bringing heavy economic burden to society and families. Therefore, it is significant to find a viable non-operative treatment to prevent and treat ligamentum flavum ossification. It should be noted that the information disclosed in the above background section is only for enhancing understanding of the background of the invention and thus may include information that does not form the prior art that is already known to those of ordinary skill in the art. Disclosure of Invention The invention aims to search possible non-operative treatment means through exploring the occurrence mechanism of the ligamentum flavum ossification, delay the occurrence and development of the ligamentum flavum ossification and achieve the purposes of early intervention and even prevention. In a first aspect of the present invention there is provided the use of irisin, or a prodrug thereof, or a degradation product thereof, or a fusion protein thereof, for the manufacture of a pharmaceutical composition for the prevention and/or treatment of yellow ligament Ossification (OLF). In another preferred embodiment, the ligamentum flavum ossification is a mechanically stimulated ligament ossification. In another preferred embodiment, the pharmaceutical composition is also used for modulating calcium signaling. In another preferred embodiment, the pharmaceutical composition is also used for limiting the extracellular calcium ion influx intensity and stabilizing the intracellular calcium ion concentration. In another preferred embodiment, the strength of the Piezo1 channel's response to mechanical stimulus is reduced. In another preferred embodiment, the pharmaceutical composition is also used for treating cell proliferation and apoptosis caused by mechanical stress. In another preferred embodiment, the pharmaceutical composition is also used for stabilizing a cell state. In another preferred embodiment, the pharmaceutical composition is also used to reduce ROS levels in cells (e.g., ligamentum flavum cells) and/or reduce cellular oxidative stress. In another preferred embodiment, the pharmaceutical composition is also used to protect mitochondrial homeostasis. In another preferred embodiment, th