MMPs but promoted Col‐II, aggrecan and PG synthesis in rat chondrocytes with or without the presence of IL‐1β and SrR

Temporomandibular joint osteoarthritis (TMJ‐OA) is a common disease with a high level of inflammation in the joint micro‐environment and cartilage degradation. Anti‐inflammation and cartilage regeneration are the key therapies for TMJ‐OA, but currently, there are no novel medi‐ cines or treatments that can control its pathogenic progression. Strontium ranelate (SrR) is an anti‐osteoporosis drug and is now considered a promising anti‐OA drug, but the anti‐inflam‐ matory effect of SrR remains to be elucidated. In the present study, the anti‐inflammatory effect of SrR in a normal or high IL‐1β environment was observed. Cell viability under the treat‐ ment of SrR was tested using Cell Counting Kit‐8. Toluidine blue staining, immunofluorescence staining, hydroxyproline assay, PCR assay and western blotting were used to detect the expression of collagen (Col)II, proteoglycans (PG) and aggrecan as a reflection of extracellular matrix synthesis and MMP‐9,13 hydroxyproline was used as an inflamma‐ tion indicator. IL‐1β of 10 ng/ml was added to the culture medium as inflammation environment and the tests of those biomarkers were done again. Then, the changes in β‐catenin were also studied by immunofluorescence staining, PCR assay and western blotting to explore the possible involvement of the Wnt/β‐catenin pathway. The results showed a significant inhibition of MMP‐9, MMP‐13, β‐catenin and promotion of Col‐II, PG and aggrecan in normal chondrocytes. The pres‐ ence of IL‐1β markedly upregulated the expression of MMP‐9, MMP‐13 and β‐catenin while suppressing Col‐II and PG and SrR partially reversed this trend. In conclusion, SrR decreased MMPs but promoted Col‐II, aggrecan and PG synthesis in rat chondrocytes with or without the presence of IL‐1β and SrR attenuated the IL‐1β‐induced increase in β‐catenin, thus reducing the inflammatory reaction. Introduction Temporomandibular disease (TMD) is one of the most common dental diseases and is characterized by temporomandibular joint (TMJ) pain, snapping and difficulty in opening the mouth, which seriously affect quality of life. There are several causes of TMJ inflammation, including abnormal biomechanical stress, injury, or systematic disease, such as rheumatoid arthritis, which result in TMD (1). TM joint osteoarthritis (TMJ‐OA) is one of the most common cases of TMD and it is typically char‐ acterized by cartilage degradation and is very difficult to cure. At present, the main pathological changes of TMJ‐OA include an increase in inflammatory factors, chondrocyte degeneration and apoptosis, matrix collagen decomposition and abnormal remodeling of subchondral bone (2). Chondrocytes are the only cell component in cartilage tissue (3). When the balance of the joint microenvironment is disturbed by factors such as abnormal stress, ageing and genetic factors, inflammatory factors such as IL‐1β, TNF‐α and nitric oxide (NO) increase (4), chondrocytes become irritated and secrete excessive MMPs, e.g. MMP‐13, aggrecanases (ADAMTS‐4, ‐5), nitric oxide synthase (iNOS) and cyclooxygenase‐2 (COX‐2), which leads to extracellular matrix (ECM) decomposition (5,6). Moreover, chondrocytes in an inflammatory state also secrete various inflammatory factors, such as IL‐1β, TNF‐α, IL‐6 and IL‐8, further leading to the aggravation of inflammation in the joint microenvironment (7). This vicious cycle of inflammation will eventually lead to cartilage destruction and the development of OA (8). A previous study emphasizes that the altered joint mechanics that cause OA are addressed in first‐line therapy, which stresses the rehabilitation of normal biomechanical and non‐inflammation microenvironments (9). Unfortunately, there are currently no pharmacological treatments or effec‐ tive interventions that can alter the joint mechanics to halt or reverse the progression of OA in the long term. As OA involves a number of pathways and risk factors, personalized therapy is the ultimate goal, which requires different targeted disease‐modifying OA drugs (DMOADs) for suitable thera‐ peutic options (10). The pool of DMOADs is always in need of growth. Strontium ranelate (SrR) is an anti‐osteoporosis drug that has the dual effect of promoting bone formation and inhibiting bone resorption and has been recently considered a possible The anti‐inflammation effect of strontium ranelate on rat chondrocytes with or without IL‐1β in vitro HAO YU1,2, YAN LIU1,2, XIANGWEN YANG1,2, JIAJING HE1,2, QUN ZHONG1,2 and XIAOJING GUO1,2 1Department of Prosthodontics, Shanghai Stomatological Hospital; 2Shanghai Key Laboratory of Craniomaxillofacial Development and Diseases, Fudan University, Huangpu, Shanghai 200001, P.R. China Received August 27, 2021; Accepted December 10, 2021 DOI: 10.3892/etm.2022. 11131 Correspondence to: Dr Xiaojing Guo, Department of Prosthodontics, Shanghai Stomatological Hospital, 356 East Beijing Road, Huangpu, Shanghai 200001, P.R. China E‐mail: guo_xiaojing@fudan.edu. cn