This "Year in Review" presents a curated selection of research themes and individual studies within the clinical osteoarthritis (OA) field, focusing on epidemiology and therapy. The search was conducted in electronic database MEDLINE from March 4, 2023, to March 31, 2024, specifically targeting English-language articles involving human participants. Inclusions were based on perceived importance and relevance to identifying risk factors or advancing OA treatments. A total of 6,539 studies were screened by the 5 authors, resulting in 157 studies considered for potential inclusion. Ultimately, 44 studies were selected, uncovering six key OA-related themes: i) the burden of OA (mostly from Global Burden of Disease studies), ii) pain drivers and trajectories, iii) impacts of sex/gender, iv) OA risk factors, and treatments for v) hand and vi) knee OA. The prevalence of OA continues to rise, particularly affecting women, with unclear distinctions in risk factors and treatment responses between sex. Associations with atopy were demonstrated in two significant databases. Notably, the authors were particularly interested in recent high-quality methodology randomised controlled trials focusing on hand (methotrexate, denosumab, colchicine, topical bethamethasone) and knee OA with conflicting results about stem cells injection. These findings collectively contribute to show the growing burden of OA, but also to help the understanding of OA pathophysiology and inform ongoing efforts to enhance management for people with OA.

Accumulation of advanced glycation end-products (AGEs) is involved in age-related osteoarthritis (OA). Glyoxalase (Glo)-1 is the main enzyme involved in the removal of AGE precursors, especially carboxymethyl-lysine (CML). We aimed to investigate the expression of several AGEs and Glo-1 in human OA cartilage and to study chondrocytic Glo-1 regulation by inflammation, mediated by interleukin (IL)-1β. Ex vivo, we quantified AGEs (pentosidine, CML, methylglyoxal-hydroimidazolone-1) in knee cartilage from 30 OA patients. Explants were also incubated with and without IL-1β, and we assessed Glo-1 protein expression and enzymatic activity. In vitro, primary cultured murine chondrocytes were stimulated with increasing concentrations of IL-1β to assess Glo-1 enzymatic activity and expression. To investigate the role of oxidative stress in the IL-1β effect, cells were also treated with inhibitors of mitochondrial oxidative stress or nitric oxide synthase. Ex vivo, only the human cartilage CML content was correlated with patient age (r = 0.78, p = 0.0031). No statistically significant correlation was found between Glo-1 protein expression and enzymatic activity in human cartilage and patient age. We observed that cartilage explant stimulation with IL-1β decreased Glo-1 protein expression and enzymatic activity. In vitro, we observed a dose-dependent decrease in Glo-1 mRNA, protein quantity, and enzymatic activity in response to IL-1β in murine chondrocytes. Inhibitors of oxidative stress blunted this downregulation. Glo-1 is impaired by inflammation mediated by IL-1β in chondrocytes through oxidative stress pathways and may explain age-dependent accumulation of the AGE CML in OA cartilage.

Beyond its effect on vegetative functions, the activation of the vagus nerve inhibits inflammation and reduces pain signaling. The aim of this open-label pilot study was to determine the efficacy and tolerance of transcutaneous auricular VNS (taVNS) on erosive hand osteoarthritis (EHOA) symptoms. Symptomatic EHOA patients with hand pain VAS ≥ 40/100 mm and ≥1 interphalangeal swollen joint(s) were included. The taVNS was performed for 4 weeks using an auricular electrode applied one hour per day and connected to a TENS device with pre-established settings. Clinical efficacy was evaluated by changes between baseline and at 4 weeks with hand pain VAS and the functional index FIHOA score, using a Wilcoxon t-test. The treatment tolerance was also evaluated. Eighteen patients (median age 69 years old, 83% women) were analyzed. At baseline, hand pain VAS was 60 mm [IQR 50; 78.2] and FIHOA 15 [10.7; 20.2]. After 4 weeks, taVNS significantly reduced hand pain VAS, with a median decrease of 23.5 mm [7.7; 37.2] (p = 0.001), as well as FIHOA, with a median decrease of 2 points [0.75; 5.2] (p = 0.01). No serious adverse events were reported. One patient stopped taVNS because of auricular discomfort. This first proof-of-concept trial indicated that taVNS is feasible and may decrease joint inflammation and clinical symptoms in EHOA, arguing for a randomized controlled study versus sham stimulation.

Objective: The non‐neuronal cholinergic system represents non‐neuronal cells that have the biochemical machinery to synthetize de novo and/or respond to acetylcholine (ACh). We undertook this study to investigate this biochemical machinery in chondrocytes and its involvement in osteoarthritis (OA).Methods: Expression of the biochemical machinery for ACh metabolism and nicotinic ACh receptors (nAChR), particularly α7‐nAChR, in human OA and murine chondrocytes was determined by polymerase chain reaction and ligand‐binding. We investigated the messenger RNA expression of the human duplicate α7‐nACh subunit, called CHRFAM7A, which is responsible for truncated α7‐nAChR. We assessed the effect of nAChR on chondrocytes activated by interleukin‐1β (IL‐1β) and the involvement of α7‐nAChR using chondrocytes from wild‐type (WT) and α7‐deficient Chrna7^−/− mice. The role of α7‐nAChR in OA was explored after medial meniscectomy in WT and Chrna7^−/− mice.Results: Human and murine chondrocytes express the biochemical partners of the non‐neuronal cholinergic system and a functional α7‐nAChR at their cell surface (n = 5 experiments with 5 samples each). The expression of CHRFAM7A in human OA chondrocytes (n = 23 samples) correlated positively with matrix metalloproteinase 3 (MMP‐3) (r = 0.38, P < 0.05) and MMP‐13 (r = 0.48, P < 0.05) expression. Nicotine decreased the IL‐1β–induced IL‐6 and MMP expression, in a dose‐dependent manner, in WT chondrocytes but not in Chrna7^−/− chondrocytes. Chrna7^−/− mice that underwent meniscectomy (n = 7) displayed more severe OA cartilage damage (mean ± SD Osteoarthritis Research Society International [OARSI] score 4.46 ± 1.09) compared to WT mice that underwent meniscectomy (n = 9) (mean ± SD OARSI score 3.05 ± 0.9; P < 0.05).Conclusion: The non‐neuronal cholinergic system is functionally expressed in chondrocytes. Stimulation of nAChR induces antiinflammatory and anticatabolic activity through α7‐nAChR, but the anticatabolic activity may be mitigated by truncated α7‐nAChR in human chondrocytes. In vivo experiments strongly suggest that α7‐nAChR has a protective role in OA.

Recent works have suggested a possible link between interleukin (IL)-33 and B-cell biology. We aimed to study the possible association between serum IL-33 detection and response to rituximab (RTX) in rheumatoid arthritis (RA) patients in different cohorts with an accurate enzyme-linked immunosorbent assay (ELISA). Serum IL-33, rheumatoid factor (RF), anti-cyclic citrullinated peptide (anti-CCP), and high serum immunoglobulin (Ig)G levels were assessed in 111 RA patients receiving a first course of 2 g RTX (cohort 1) in an observational study and in 74 RA patients treated with the same schedule in routine care (cohort 2). Univariate and multivariate analyses identified factors associated with a European League Against Rheumatism (EULAR) response at 24 weeks. At week 24, 84/111 (76%) and 54/74 (73%) patients reached EULAR response in cohorts 1 and 2, respectively. Serum IL-33 was detectable in only 33.5% of the patients. In the combined cohorts, the presence of RF or anti-CCP (odds ratio (OR) 3.27, 95% confidence interval (CI) 1.13–9.46; p = 0.03), high serum IgG (OR 2.32, 95% CI 1.01–5.33; p = 0.048), and detectable serum IL-33 (OR 2.40, 95% CI 1.01–5.72; p = 0.047) were all associated with RTX response in multivariate analysis. The combination of these three factors increased the likelihood of response to RTX. When serum IL-33 detection was added to seropositivity and serum IgG level, 100% of the patients with the three risk factors (corresponding to 9% of the population) responded to RTX (OR versus patients with none of the three risk factors 29.61, 95% CI 1.30–674.79; p = 0.034). Detectable serum IL-33 may predict clinical response to RTX independently of, and synergistically with, auto-antibodies and serum IgG level. NCT01126541 ; 18 May 2010.