Biomolecules

Review

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13 pages, 17084 KiB

Open AccessReview

Effects of β2 Integrins on Osteoclasts, Macrophages, Chondrocytes, and Synovial Fibroblasts in Osteoarthritis

by Tiantian Hu, Zhan Zhang, Chunbo Deng, Xun Ma and Xueyong Liu

Biomolecules 2022, 12(11), 1653; https://doi.org/10.3390/biom12111653 - 08 Nov 2022

Cited by 6 | Viewed by 1958

Abstract

β2 integrins are transmembrane receptors that exist widely in human immune cells and participate in pathological processes such as chronic inflammation, thrombosis, and malignant tumor formation. They mainly mediate intercellular adhesion, coordinate the ingestion of extracellular matrix components, and regulate cytoskeleton formation, thereby [...] Read more.

β2 integrins are transmembrane receptors that exist widely in human immune cells and participate in pathological processes such as chronic inflammation, thrombosis, and malignant tumor formation. They mainly mediate intercellular adhesion, coordinate the ingestion of extracellular matrix components, and regulate cytoskeleton formation, thereby regulating cell signaling. Osteoarthritis (OA) is a chronic joint disease that causes joint pain and increases disease burden; it has a high prevalence among populations worldwide. Previous studies have reported that β2 integrins are overexpressed in OA and may play an essential role in the occurrence of OA. The important roles of β2 integrins in the maturation and differentiation of osteoclasts, the regulation of bone homeostasis, and the polarization and migration of macrophages have also been reported. The present review aims to highlight the role of β2 integrins in OA pathogenesis and outline their potential for serving as therapeutic targets. Full article

(This article belongs to the Special Issue Advances in Inflammatory Arthritis and Myositis)

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16 pages, 738 KiB

Open AccessReview

Targeting Toll-like Receptor (TLR) Pathways in Inflammatory Arthritis: Two Better Than One?

by Sandra Santos-Sierra

Biomolecules 2021, 11(9), 1291; https://doi.org/10.3390/biom11091291 - 30 Aug 2021

Cited by 13 | Viewed by 5804

Abstract

Inflammatory arthritis is a cluster of diseases caused by unregulated activity of the immune system. The lost homeostasis is followed by the immune attack of one’s self, what damages healthy cells and tissues and leads to chronic inflammation of various tissues and organs [...] Read more.

Inflammatory arthritis is a cluster of diseases caused by unregulated activity of the immune system. The lost homeostasis is followed by the immune attack of one’s self, what damages healthy cells and tissues and leads to chronic inflammation of various tissues and organs (e.g., joints, lungs, heart, eyes). Different medications to control the excessive immune response are in use, however, drug resistances, flare-reactions and adverse effects to the current therapies are common in the affected patients. Thus, it is essential to broaden the spectrum of alternative treatments and to develop disease-modifying drugs. In the last 20 years, the involvement of the innate immune receptors TLRs in inflammatory arthritis has been widely investigated and targeting either the receptor itself or the proteins in the downstream signalling cascades has emerged as a promising therapeutic strategy. Yet, concerns about the use of pharmacological agents that inhibit TLR activity and may leave the host unprotected against invading pathogens and toxicity issues amid inhibition of downstream kinases crucial in various cellular functions have arisen. This review summarizes the existing knowledge on the role of TLRs in inflammatory arthritis; in addition, the likely druggable related targets and the developed inhibitors, and discusses the pros and cons of their potential clinical use. Full article

(This article belongs to the Special Issue Advances in Inflammatory Arthritis and Myositis)

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Other

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13 pages, 1184 KiB

Open AccessSystematic Review

by Ratna Shree Sharma, Johannes Pallua and Michael Schirmer

Biomolecules 2022, 12(2), 303; https://doi.org/10.3390/biom12020303 - 14 Feb 2022

Viewed by 2331

Abstract

Prospective, double-blind, randomized, placebo-controlled studies are considered to provide the highest quality of interventional evidence. This meta-analysis summarizes the frequencies of adverse events according to the Medical Dictionary for Regulatory Activities (MedDRA) in the placebo arms of 101 such studies in rheumatoid arthritis, [...] Read more.

Prospective, double-blind, randomized, placebo-controlled studies are considered to provide the highest quality of interventional evidence. This meta-analysis summarizes the frequencies of adverse events according to the Medical Dictionary for Regulatory Activities (MedDRA) in the placebo arms of 101 such studies in rheumatoid arthritis, including a total of 17,150 patients in the placebo arms and 37,819 patients in the verum arms. Placebo-treated patients reported more than one adverse event in a median of 55.0%, 65.5%, and 72.5% (compared to 72.3% in the verum arms), and a serious adverse event in 2.5%, 5.8%, and 8.6% (compared to 5.9% in the verum arms), with stable doses of corticosteroids, conventional synthetic disease-modifying antirheumatic drugs (DMARDs), and biological DMARDs as background therapies, respectively. Odds ratios were comparable between placebo and verum arms for nausea (1.00 with 95% confidence interval (CI) 0.86–1.17), for hepatobiliary disorders (1.08 with CI 0.85–1.36), for abnormal hepatic functions (1.09 with CI 0.83–1.44), and general disorders and administration site conditions (1.39 with CI 0.95–2.03). A publication bias has to be assumed for nausea (p = 0.018; Egger’s test), diarrhoea (p = 0.022), and serious infections and infestations (p = 0.009). In conclusion, patients should be aware that “adverse events” may occur even with placebo medication, independent from an additional verum medication added to the background therapy. Further studies are warranted to respect and overcome the psychological and other issues related to these placebo-related “adverse events”. Full article

(This article belongs to the Special Issue Advances in Inflammatory Arthritis and Myositis)

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