J o u r n a l P r e -p r o o f Journal Pre-proof 2

Introduction Osteoarthritis (OA) is a degenerative joint disease characterized by articular cartilage degradation, subchondral damage, and bone remodelling, affecting most commonly weight-bearing joints, such as the knee and hip. The loss of cartilage leads to joint space narrowing, pain, and loss of function which could ultimately require total joint replacement. The Wnt/β catenin pathway is involved in the pathophysiology of OA and has been proposed as a therapeutic target. Endogenous and pharmacological inhibitors of this pathway were recently investigated within innovative therapies including the use of platelet-rich plasma (PRP) and mesenchymal stem cells (MSCs). Methods A review of the literature was performed on the PubMed database based on the following inclusion criteria: article written in English language in the last 20 years and dealing with (1) the role of Wnt-β catenin pathway in the pathogenesis of osteoarthritis and (2) pharmacologic or biologic strategies modulating the Wnt-β catenin pathway in the OA setting. Results Evidences support that Wnt signalling pathway is likely linked to OA progression and severity. Its inhibition through natural antagonists and new synthetic or biological drugs shares the potential to improve the clinical condition of the patients by affecting the pathological activity of Wnt/β-catenin signalling. Conclusions While further research is needed to better understand the mechanisms regulating the molecular interaction between OA regenerative therapies and Wnt, it seems that biologic therapies for OA exert modulation on Wnt/β catenin pathway that might be relevant in achieving the beneficial clinical effect of those therapeutic strategies.

Background: Agreement on how to identify psoriasis (PsO) patients at risk of developing psoriatic arthritis (PsA) is lacking. Objective: To identify predictors, risk factors and incidence rate (IR) of PsA development in PsO patients through a systematic literature review (SLR) and meta-analyses (MA).Methods: MEDLINE, Embase, and Cochrane databases were searched. Cohort studies were used to assess the predictors, while case-control studies for PsA risk factor determination. Results: We screened 4698 articles for eligibility, and 110 underwent a full reading and 26 were finally included. Among skin and nail phenotypes, PsO severity and nail pitting were selected as predictors of PsA development. Furthermore, PsO patients with arthralgia (pooled RR 2.15 [1.16; 3.99]) and/or with imaging-MSK inflammation (pooled RR 3.72 [2.12; 6.51]) were at high risk of PsA. Higher categories of BMI and a family history of PsA were other predictors. In

Rationale: COVID-19 presentation is multifaceted and up to 44% of patients affected by COVID-19 experience musculoskeletal complaints, mostly in the form of diffuse aspecific arthromyalgias. Nevertheless, only a few cases of arthritis following SARS-CoV2 infection are reported. Patient concerns: A 27-year-old man affected by nail psoriasis presented with monoarthritis 2 weeks after being diagnosed with COVID-19. Diagnoses: Diagnostic work-up and differential diagnosis were made difficult by patient isolation, absence of lab tests, and his visit via telemedicine, even though signs of first metacarpophalangeal joint involvement were clear. Interventions: Due to the inefficacy of acetaminophen and nonsteroidal anti-inflammatory drugs, the patient was prescribed oral steroids with a rapid benefit. Outcomes: The patient's response to oral steroid was prompt and maintained even after therapy tapering. Even so, a formal diagnosis was not possible due to a difficult diagnostic work-up and lack of a long-term follow-up. Lessons: Like many other viral diseases, SARS-CoV2 can play as a causative agent or as a trigger for inflammatory arthritis development in predisposed individuals.

Summary Tofacitinib is an oral small molecule targeting the intracellular Janus kinase–signal transducer and activator of transcription (JAK-STAT) pathways approved for the treatment of active rheumatoid arthritis (RA). We investigated the effects of tofacitinib on the response of RA lymphocytes to B and T cell collagen epitopes in their native and post-translationally modified forms. In particular, peripheral blood mononuclear cells (PBMCs) from patients with RA and healthy subjects were cultured with type II collagen peptides (T261-273, B359-369, carT261-273, citB359-369) or with phorbol myristate acetate (PMA)/ionomycin/CD40L in the presence or absence of 100 nM tofacitinib for 20 h and analyzed by fluorescence activated cell sorter (FACS). Cultures without brefeldin A were used for cytokine supernatant enzyme-linked immunosorbent assay (ELISA) analysis. Tofacitinib down-regulated inflammatory cytokines by stimulated B [interleukin (IL)-6 and tumor necrosis factor (TNF)-α] and T [interferon (IFN)-γ, IL-17 or TNF-α] cells in the short term, while a significant reduction of IL-17 and IL-6 levels in peripheral blood mononuclear cell (PBMC) supernatant was also observed. IL-10 was significantly reduced in collagen-stimulated B cells from patients with RA and increased in controls, thus mirroring an altered response to collagen self-epitopes in RA. Tofacitinib partially prevented the IL-10 down-modulation in RA B cells stimulated with collagen epitopes. In conclusion, the use of tofacitinib exerts a rapid regulatory effect on B cells from patients with RA following stimulation with collagen epitopes while not reducing inflammatory cytokine production by lymphocytes.