Acetyl-11-Keto-β-Boswellic Acid Restrains Inflammation and Extracellular Matrix Degradation of Osteoarthritis via Suppression of NF-κB Pathway

Abstract

Background: Mechanical stress along with inflammation play causative roles in the development of osteoarthritis (OA), which decreases the quality of life and causes economic loss. Inflammation and extracellular matrix (ECM) degradation have been identified as key factors in the development of OA. As the main active component in frankincense, acetyl-11-keto-β-boswellic acid (AKBA) has been shown to have positive effects on inflammation. However, the effects of AKBA in cartilage inflammation and ECM degradation are currently elusive. \n \nMethods: Micro-CT, Histologic analysis, and Immunohistochemical (IHC) analysis were conducted in vivo on Hulth-Telhag OA rat with or without AKBA treatment. The effects of AKBA on inflammation and ECM degradation of rat articular chondrocytes were evaluated by CCK-8, Western Blot, quantitative real-time polymerase chain reaction (qRT-PCR), and immunofluorescence (IF) assay. We demonstrated the role of inflammation and ECM degradation in the pathogenesis of OA and determined the protective effect of AKBA on both Hulth-Telhag rat OA model and lipopolysaccharide (LPS)-induced rat chondrocytes. \n \nFindings: We found increased inflammatory expression and decreased ECM expression in OA model cartilage and LPS-induced chondrocytes. Meanwhile, the protective effect of AKBA and its inhibitory effects on inflammation as well as ECM-related markers were also observed in the rat Hulth-Telhag model. Furthermore, activation of NF-κB attenuated nuclear p65 protein levels in chondrocytes upon LPS stimulation. In addition, AKBA was found to subsequently reversed the LPS-induced activation of NF- κB signal and inflammation-related ECM degradation in chondrocytes. \n \nInterpretation: Suppression of NF-κB pathway activation by AKBA restrains OA development via inhibition of inflammation and ECM degradation. AKBA is a promising therapeutic agent for the treatment of OA. \n \nFunding Information: Financial supports from National Natural Science Foundation of China (Nos. 82072425, 81873991 and 81672238), the Natural Science Foundation of Jiangsu Province (Nos. BK20180001), Jiangsu Commission of Health (No. H2018027); the Young Medical Talents of Jiangsu Province (No. QNRC2016751), Suzhou Jiangsu Commission of Health (No. SYS2019100 and SYS2019101), Suzhou Science and Technology Foundation (No. SYSD2017170, SYSD2018207 and SS201805), Project of Suzhou Sports Research Bureau (No. TY2019-204), and Special Project of Diagnosis and Treatment Technology for Key Clinical Diseases in Suzhou (LCZX202003). \n \nDeclaration of Interests: There are no declarations of interest. \n \nEthics Approval Statement: Animal welfare and experimental procedures were carried out in accordance with the Declaration of Helsinki, and were approved by the Ethics Committee of the First Affiliated Hospital of Soochow University.