The final, formatted version of the article will be published soon.
ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Ethnopharmacology
Volume 16 - 2025 |
doi: 10.3389/fphar.2025.1517221
This article is part of the Research Topic Herbal Medicines and Their Metabolites as Therapeutic Agents in Osteolytic Disease Management View all 6 articles
Myristic Acid Beneficially Modulates Intervertebral Disc Degeneration by Preventing Endplate Osteochondral Remodeling and Vertebral Osteoporosis in Naturally Aged Mice
Provisionally accepted
Yan Gong 1* Yuzhuo Zhang 2* Xingda Chen 1*
Zelin Zhou 1 Weicheng Qin 1* Yanchi Gan 3*
Jiahui He 4 Jizhi Ma 1* Guifeng Chen 5*
Qi Shang 2 Kai Tang 1* Honglin Chen 1* Yu Liu 1* De Liang 1* Gengyang Shen 2*
Xiaobing Jiang 2*
Zhaojun Cheng 1*- 1 The First Affiliated Hospital of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, China
- 2 The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong Province, China
- 3 Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine, Nanning, Guangxi Zhuang Region, China
- 4 The Affiliated TCM Hospital of Guangzhou Medical University, Guangzhou, China
- 5 School of Medicine, Shanghai Jiao Tong University, Shanghai, Shanghai Municipality, China
Background:The origin of intervertebral disc degeneration (IDD) is highly complex, where both cartilage endplate remodeling and vertebral osteoporosis are of utmost importance. Myristic acid (MA), a saturated fatty acid derived from nutmeg, a traditional Chinese herb, has been shown to boost memory. Additionally, its isomers have been verified to have anti-osteoporotic characteristics.However, the precise mechanism by which MA functions in relation to IDD remains unclear. Methods: In vivo, a natural aging animal model was used. The drug -administration method of MA was intraperitoneal injection to mice aged 22 months at a dose of 2 mg/kg•d for two months. Micro-CT observed vertebral bone mass and endplate changes, followed by Hematoxylineosin (H&E), Masson, and Safranin-O staining of tissues. TRAP staining counted osteoclasts; immunohistochemistry detected the expressions of Aggrecan and Collagen II. Bioinformatics explored MA's anti-IDD mechanism. In vitro, MA-treated senescent endplate chondrocytes (induced by TBHP) were analyzed by Real-Time PCR (qPCR) and immunofluorescence (IF) for senescence and matrix synthesis markers. TRAP and F-actin detected MA's effect on RAW264.7 osteoclast differentiation (induced by RANKL); qPCR examined the expressions of osteoclast genes. Results: Using the natural aging model, we found that MA tended to improve vertebral osteoporosis and endplate osteochondral remodeling, decreased the TRAP activity of the endplate, and alleviated IDD in naturally aging mice. Bioinformatics analysis suggested that the relationships among IDD, osteoporosis, and endplate degeneration were mainly linked to cellular senescence. In vitro, MA postponed the senescence of TBHP-induced endplate chondrocytes by increasing the expression of aggrecan and decreasing the expressions of MMP-3, MMP-9, and the senescence markers p16 and p21. Additionally, MA notably inhibited osteoclast activity, as evidenced by a decrease in the number of osteoclasts and a significant suppression of F-actin formation. At the molecular level, MA efficiently reduced the expressions of osteoclast marker genes like ACP-5, CTSK, and DC-STAMP. Conclusion: The findings of this research suggest that MA is capable of inhibiting endplate osteochondral remodeling and vertebral osteoporosis, diminishing osteoclastogenesis to preserve bone mass, and consequently delaying IDD in naturally aging mice. Hence, MA holds the potential to serve as an alternative therapeutic approach for IDD.
Keywords: Myristic Acid, endplate chondrocytes, Osteoporosis, endplate osteochondral remodeling, Intervertebral Disc Degeneration
Received: 25 Oct 2024; Accepted: 10 Jan 2025.
Copyright: © 2025 Gong, Zhang, Chen, Zhou, Qin, Gan, He, Ma, Chen, Shang, Tang, Chen, Liu, Liang, Shen, Jiang and Cheng. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Yan Gong, The First Affiliated Hospital of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, China
Yuzhuo Zhang, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510260, Guangdong Province, China
Xingda Chen, The First Affiliated Hospital of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, China
Weicheng Qin, The First Affiliated Hospital of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, China
Yanchi Gan, Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine, Nanning, 530031, Guangxi Zhuang Region, China
Jizhi Ma, The First Affiliated Hospital of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, China
Guifeng Chen, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200025, Shanghai Municipality, China
Kai Tang, The First Affiliated Hospital of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, China
Honglin Chen, The First Affiliated Hospital of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, China
Yu Liu, The First Affiliated Hospital of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, China
De Liang, The First Affiliated Hospital of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, China
Gengyang Shen, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510260, Guangdong Province, China
Xiaobing Jiang, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510260, Guangdong Province, China
Zhaojun Cheng, The First Affiliated Hospital of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, China
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.