synovial inflammation
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2022 ◽  
Vol 12 ◽  
Author(s):  
Gundula Rösch ◽  
Dominique Muschter ◽  
Shahed Taheri ◽  
Karima El Bagdadi ◽  
Christoph Dorn ◽  
...  

PurposeRecent studies demonstrated a contribution of adrenoceptors (ARs) to osteoarthritis (OA) pathogenesis. Several AR subtypes are expressed in joint tissues and the β2-AR subtype seems to play a major role during OA progression. However, the importance of β2-AR has not yet been investigated in knee OA. Therefore, we examined the development of knee OA in β2-AR-deficient (Adrb2-/-) mice after surgical OA induction.MethodsOA was induced by destabilization of the medial meniscus (DMM) in male wildtype (WT) and Adrb2-/- mice. Cartilage degeneration and synovial inflammation were evaluated by histological scoring. Subchondral bone remodeling was analyzed using micro-CT. Osteoblast (alkaline phosphatase - ALP) and osteoclast (cathepsin K - CatK) activity were analyzed by immunostainings. To evaluate β2-AR deficiency-associated effects, body weight, sympathetic tone (splenic norepinephrine (NE) via HPLC) and serum leptin levels (ELISA) were determined. Expression of the second major AR, the α2-AR, was analyzed in joint tissues by immunostaining.ResultsWT and Adrb2-/- DMM mice developed comparable changes in cartilage degeneration and synovial inflammation. Adrb2-/- DMM mice displayed elevated calcified cartilage and subchondral bone plate thickness as well as increased epiphyseal BV/TV compared to WTs, while there were no significant differences in Sham animals. In the subchondral bone of Adrb2-/- mice, osteoblasts activity increased and osteoclast activity deceased. Adrb2-/- mice had significantly higher body weight and fat mass compared to WT mice. Serum leptin levels increased in Adrb2-/- DMM compared to WT DMM without any difference between the respective Shams. There was no difference in the development of meniscal ossicles and osteophytes or in the subarticular trabecular microstructure between Adrb2-/- and WT DMM as well as Adrb2-/- and WT Sham mice. Number of α2-AR-positive cells was lower in Adrb2-/- than in WT mice in all analyzed tissues and decreased in both Adrb2-/- and WT over time.ConclusionWe propose that the increased bone mass in Adrb2-/- DMM mice was not only due to β2-AR deficiency but to a synergistic effect of OA and elevated leptin concentrations. Taken together, β2-AR plays a major role in OA-related subchondral bone remodeling and is thus an attractive target for the exploration of novel therapeutic avenues.


2022 ◽  
Vol 12 ◽  
Author(s):  
Nanxing Yi ◽  
Yilin Mi ◽  
Xiaotong Xu ◽  
Naping Li ◽  
Fan Zeng ◽  
...  

As life expectancy increases, Osteoarthritis (OA) is becoming a more frequently seen chronic joint disease. The main characteristics of OA are loss of articular cartilage, subchondral bone sclerosis, and synovial inflammation. Baicalein (Bai), a traditional Chinese medicine extracted from Scutellaria baicalensis Georgi, has been demonstrated to exert notable anti-inflammatory effects in previous studies, suggesting its potential effect in the treatment of OA. In this study, we first predicted the action targets of Bai, mapped target genes related to OA, identified potential anti-OA targets for Bai, performed gene ontology (GO) enrichment, and KEGG signaling pathway analyses of the action targets, and analyzed the molecular docking of key Bai targets. Additionally, the effect and potential mechanism of Bai against OA were verified in mouse knee OA models induced by destabilized medial meniscus (DMM) surgery. GO and KEGG analyses showed that 19 anti-OA targets were mainly involved in the response to oxidative stress, the response to hypoxia and apoptosis, and the PI3K-Akt and p53 signaling pathways. Molecular docking results indicated that BAX, BCL 2, and Caspase 3 enriched in the apoptotic signaling pathway have high binding affinity with Bai. Validation experiments showed that Bai can significantly attenuate the loss of articular cartilage (OARSI score), suppress synovial inflammation (synovitis score), and ameliorate subchondral bone resorption measured by micro-CT. In addition, Bai notably inhibited the expression of apoptosis-related proteins in articular cartilage (BAX, BCL 2, and Caspase 3). By combining network pharmacology with experimental validation, our study identifies and verifies the importance of the apoptotic signaling pathway in the treatment of OA by Bai. Bai may have promising application and potential therapeutic value in OA treatment.


2022 ◽  
Author(s):  
Steven Guan ◽  
Bella Mehta ◽  
David Slater ◽  
James R. Thompson ◽  
Edward DiCarlo ◽  
...  

2022 ◽  
Author(s):  
Rui-bo Guo ◽  
Xin-yue Zhang ◽  
De-kang Yan ◽  
Ying-jie Yu ◽  
Yu-jia Wang ◽  
...  

Rheumatoid arthritis (RA) is an autoimmune disease characterized by hyperplasia of synovial, inflammation of joints, erosion of cartilage and bone destruction. Macrophages play an essential role in the pathogenesis of...


2021 ◽  
Vol 12 ◽  
Author(s):  
Huijie Zhang ◽  
Juan Liu ◽  
Pingxin Zhang ◽  
Dongyang Li ◽  
Guiyu Feng ◽  
...  

The etiology and pathogenesis of rheumatoid arthritis (RA) have not yet been fully elucidated, with greater adverse drug effects in traditional treatment of RA. It is particularly necessary to develop and study Chinese herbal formula as a supplement and alternative drug for the treatment of RA. The traditional Chinese medicine compound Longteng Decoction (LTD), as an empirical prescription in the treatment of RA in Dongzhimen Hospital of Beijing University of Chinese Medicine, has been widely used in clinic. Type 2 innate lymphocytes (ILC2s) have specific transcription factors and signature cytokines that are very similar to Th cells, which have been proved to be necessary in addressing RA inflammation, and are potential targets for RA prevention and treatment. Our previous studies have confirmed that LTD can intervene in the differentiation of peripheral blood Th17 and Treg cells, reduce joint pain index and swelling degree, shorten the time of morning stiffness, reduce ESR, and inhibit joint inflammation. However, it is unclear whether LTD can promote the regression of RA synovial inflammation by regulating the immune response mechanism of ILC2s.Therefore, our team established a collagen-induced arthritis mouse model and conducted an experimental study with LTD as the intervention object. The results showed that joint swelling, synovial inflammatory infiltration, and articular cartilage destruction were alleviated in CIA mice after intervention with LTD. The proliferation and differentiation of Th17 inflammatory cells and the secretion of proinflammatory cytokines (IL-17 and IFN-γ) were inhibited. In addition, LTD can also activate ILC2s to secrete the anti-inflammatory cytokine IL-4, activate the STAT6 signaling pathway, and act synergistic with Treg cells to inhibit the infiltration of type M1 macrophages in synovial tissue and promote its transformation to M2 phenotype. Taken together, these results confirm that LTD can be used as an adjunct or alternative to RA therapy by modulating the ILC2s immune response network and slowing down the inflammatory process of synovial tissue.


Author(s):  
Hayri Ogul ◽  
Bahar Cankaya ◽  
Mecit Kantarci

Loose bodies (LBs) are intraarticular free bodies that result from various pathological processes and cause synovial inflammation. Timely and complete identification of LBs is important for appropriate treatment and prevention of possible complications such as osteoarthritis. LBs in the ankle joint can reach all the compartments that are adjacent to the joint via physiological or pathological connections. The presence, localisation, and number of LBs in the ankle joint and adjacent synovial compartments can be optimally evaluated using high-resolution magnetic resonance arthrography (MRA) and computed tomography arthrography (CTA). On this review article, we aimed to determine the LB location and distribution using high-resolution MRA and CTA of the ankle joint, and to demonstrate that it may be used as a complementary examination to guide interventional arthroscopy in difficult-to-reach areas during treatment. Advances in knowledge Loose bodies (LBs) are intraarticular free bodies and may cause synovial inflammation. Accurate and complete determination of the number and location of LBs before surgery are very important for effective treatment. The location, number and distribution of LBs in the ankle joint may be determined successfully by high-resolution magnetic resonance arthrography (MRA) and computed tomography arthrography (CTA). For this purpose, MRA and CTA may increase the diagnostic and therapeutic success of the arthroscopy.


JCI Insight ◽  
2021 ◽  
Vol 6 (23) ◽  
Author(s):  
Jingnan Wang ◽  
Chuyu Shen ◽  
Ruiru Li ◽  
Cuicui Wang ◽  
Youjun Xiao ◽  
...  

2021 ◽  
Vol 101 ◽  
pp. 108310
Author(s):  
Dongyi Wang ◽  
Fan Yang ◽  
Wei Shang ◽  
Zhiming Zhao ◽  
Junyi Shen ◽  
...  

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