The Wnt signaling pathway plays a key role in several biological processes, such as cellular proliferation and tissue regeneration, and its dysregulation is involved in the pathogenesis of many autoimmune diseases. Several evidences support its role especially in bone complications of rheumatic diseases. In Rheumatoid Arthritis (RA), the Wnt signaling is implicated in systemic and localized bone loss, while available data of its role in Spondyloarthritis (SpA) are conflicting. In the last few decades, the quality of life of rheumatic patients has been dramatically improved by biological therapy, targeting cytokines involved in the pathogenesis of these diseases like tumor necrosis factor (TNF)α, interleukin (IL)-1, IL-6, IL-17. In this review, we reviewed the role of Wnt signaling in RA and SpA, focusing on the effect of biological therapy on this pathway and its possible clinical implications.

A decline in bone mass leading to an increased fracture risk is a common feature of age-related bone changes. The mechanisms underlying bone senescence are very complex and implicate systemic and local factors and are the result of the combination of several changes occurring at the cellular, tissue and structural levels; they include alterations of bone cell differentiation and activity, oxidative stress, genetic damage and the altered responses of bone cells to various biological signals and to mechanical loading. The molecular mechanisms responsible for these changes remain greatly unclear and many data derived from in vitro or animal studies appear to be conflicting and heterogeneous, probably due to the different experimental approaches; nevertheless, understanding the main physio-pathological processes that cause bone senescence is essential for the development of new potential therapeutic options for treating age-related bone loss. This article reviews the current knowledge concerning the molecular mechanisms underlying the pathogenesis of age-related bone changes.

Natural products have been used in medicine for thousands of years. Given their potential health benefits, they have gained significant popularity in recent times. The administration of phytochemicals existed shown to regulate differential gene expression and modulate various cellular pathways implicated in cell protection. Curcumin is a natural dietary polyphenol extracted from Curcuma Longa Linn with different biological and pharmacological effects. One of the important targets of curcumin is Toll-like receptor-4 (TLR-4), the receptor which plays a key role in the modulation of the immune responses and the stimulation of inflammatory chemokines and cytokines production. Different studies have demonstrated that curcumin attenuates inflammatory response via TLR-4 acting directly on receptor, or by its downstream pathway. Curcumin bioavailability is low, so the use of exosomes, as nano drug delivery, could improve the efficacy of curcumin in inflammatory diseases. The focus of this review is to explore the therapeutic effect of curcumin interacting with TLR-4 receptor and how this modulation could improve the prognosis of neuroinflammatory and rheumatic diseases.

An increased risk of developing severe infections has been evidenced in rheumatic disease (RD) patients, and anti-COVID-19 vaccination is strictly recommended for RD patients. However, up to now, no data are available on safety, immunogenicity and efficacy of COVID-19 vaccinations in RD patients. The possible development of adverse events (AEs), including the flare-up of underlying RD, represents a matter of growing importance. The aim of our study is to assess, in RD patients, the safety profile of different types of approved vaccines and the possible influence of immunosuppressive therapies and clinical or demographic characteristics of RD patients on development of AEs. Participants (n = 185; 30.7%) received anti-COVID-19 vaccinations, 137 with autoimmune/chronic inflammatory RD (Au/cIn-RD) and 48 with nonautoimmune/chronic inflammatory RD (no-Au/cIn-RD). AEs were recorded in 42% of patients after the first dose of vaccine, and in 26% of patients after the second dose. The most common reported AEs after anti-COVID 19 vaccines were site injection pain (17%), headache (12%), fever (12%), myalgia (10%) and fatigue (10%). Relapses of the underlying Au/c-In-RD were recorded in 2.2% of patients after the first dose of vaccine. In Au/c-In-RD the risk of developing AEs after the first dose of vaccine was lower in older patients (OR = 0.95; p = 0.001), and in the group of patients with complete control of RD (OR: 0.2; p = 0.010). A lower percentage of AEs was observed in patients with complete control of their Au/cIn-RD (29%) compared to those with low (57%) or moderate-high disease activity (63%) (p = 0.002 and p = 0.006 respectively). In this study all types of COVID-19 vaccines in use in Italy seemed safe in RD patients. The results of this study might provide reassuring information for Au/cIn RD patients and clinicians and could strengthen the data on vaccine safety to guide the use of COVID-19 vaccines in Au/cIn-RD on immunosuppressive agents.

JAK/STAT signaling pathway is involved in many diseases, including autoimmune diseases, which are characterized by a close interconnection between immune and bone system. JAK/STAT pathway is involved in bone homeostasis and plays an important role in proliferation and differentiation of some cell types, including osteoblasts and osteoclasts. Different molecules, such as cytokines, hormones, and growth factors are responsible for the activation of the JAK/STAT pathway, which leads, at the nuclear level, to start DNA transcription of target genes. Bone cells and remodeling process are often influenced by many cytokines, which act as strong stimulators of bone formation and resorption. Our aim, through careful research in literature, has been to provide an overview of the role of the JAK/STAT pathway in bone remodeling and on bone cells, with a focus on cytokines involved in bone turnover through this signal cascade. The JAK/STAT pathway, through the signal cascade activation mediated by the interaction with many cytokines, acts on bone cells and appears to be involved in bone remodeling process. However, many other studies are needed to completely understand the molecular mechanism underlying these bone process.