Research Paper Volume 14, Issue 16 pp 6716—6726
Psoralen downregulates osteoarthritis chondrocyte inflammation via an estrogen-like effect and attenuates osteoarthritis
- 1 Departments of Orthopedics, The First Hospital of Yangtze University, Jingzhou, China
- 2 Departments of Orthopedics, The Jiangling County People’s Hospital, Jingzhou, China
- 3 The Second Affiliated Hospital, Guangdong Provincial Key Laboratory of Allergy and Clinical Immunology, The State Key Laboratory of Respiratory Disease, Guangzhou Medical University, Guangzhou, China
- 4 Department of Biotechnology, University of Science and Technology, Bannu, Pakistan
- 5 Department of Biochemistry and Molecular Biology, Quaid-i-Azam University, Islamabad, Pakistan
Received: May 5, 2022 Accepted: August 3, 2022 Published: August 24, 2022
https://doi.org/10.18632/aging.204245How to Cite
Copyright: © 2022 Huang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Estrogen and its receptor play a positive role in the development of osteoarthritis (OA). Psoralen is a plant-derived estrogen analog. This study aimed to verify whether psoralen inhibits OA through an estrogen-like effect. First, human primary chondrocytes in the late stage of OA were extracted to complete collagen type II immunofluorescence staining and cell proliferation experiments. Subsequently, estrogen, psoralen and estrogen receptor antagonists were co-cultured with OA chondrocytes, and RT-PCR was performed to detect the gene expression. A rabbit OA model was subsequently made by anterior cruciate ligament transection (ACLT). They were set as Sham group, OA group and Psoralen group, respectively. The articular cartilage samples were taken after 5 weeks of treatment, and the effect was observed by gross observation, histological staining, micro-CT scanning of subchondral bone. The results of cellular experiments displayed that the cultured cells were positive for collagen II fluorescence staining and 12 μg/mL psoralen was selected as the optimal concentration. In addition, psoralen had effects similar to estrogen, promoting the expression of estrogen tar-get genes CTSD, PGR and TFF1 and decreasing the expression of the inflammation-related gene TNF- α, IL-1β and IL-6. The effect of psoralen was blocked after the use of an estrogen receptor antagonist. Further animal experiments indicated that the psoralen group showed less destruction of cartilage tissue and decreased OASRI scores compared with the OA group. A subchondral bone CT scan demonstrated that psoralen significantly increased subchondral bone mineral density (BMD), trabecular thickness and trabecular number and decreased trabecular separation. In summary, psoralen inhibits the inflammatory production of chondrocytes, which is related to estrogen-like effect, and can be used to attenuate the progression of OA.