Psoralen downregulates osteoarthritis chondrocyte inflammation via an estrogen-like effect and attenuates osteoarthritis

Abstract

Estrogen and its receptor play a positive role in the development of osteoarthritis (OA). Psoralen is a plantderived 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.Abstract image. Psoralen inhibits the inflammatory production of chondrocytes, which is related to estrogen-like effect, and can be used to attenuate the progression of OA.

Effect of Osteoporosis Treatments on Osteoarthritis Progression in Postmenopausal Women: A Review of the Literature

“…Studies using animal models of a postmenopausal state and decreased estrogen level have indicated that maintaining a normal physiologic estrogen level can reduce OA symptoms [ 11 – 13 ]. Xu et el.…”

“…Psoralen is an estrogen analog that is derived from plants. Huang et al [ 13 ] studied the effects of psoralen in a rabbit OA model that was created by transection of the anterior cruciate ligament. The results showed that psoralen decreased the destruction of cartilage tissue reflected by Osteoarthritis Research Society International (OARSI) score and increased subchondral BMD, trabecular thickness and number.…”

Colon-targeted oral nanoliposomes loaded with psoralen alleviate DSS-induced ulcerative colitis

“…Research indicates that psoralen exhibits a range of pharmacological activities, including anti-photoaging, anti-inflammatory, antioxidant, and immune regulation properties. [15][16][17] Due to its photosensitivity, psoralen combined with UVA photochemotherapy is an effective method for clinical treatment of psoriasis. Psoralen also has phototoxic and photocarcinogenic effects, it can insert into DNA and induce photochemical mutations, ultimately leading to cell damage, cell death, mutations, and even causing diseases such as skin cancer.…”