Nature Reviews Rheumatology最新文献

{"title":"Peripheral neuronal sensitization and neurovascular remodelling in osteoarthritis pain","authors":"Vicky Batchelor, Thomas A. Perry, M. Zameel Cader, Tonia L. Vincent","doi":"10.1038/s41584-025-01280-3","DOIUrl":"10.1038/s41584-025-01280-3","url":null,"abstract":"Pain is the primary complaint in individuals with osteoarthritis (OA) and changes as the disease progresses. Anatomical changes in several joint structures potentially contribute to pain, including the increased innervation of the periosteum, synovium and subchondral bone, and the pathological innervation of articular cartilage, which is aneural under physiological conditions. Research has focused on molecules that sensitize afferent neurons, such as neuropeptides, neurotrophins, pro-inflammatory cytokines and ion channels. The neurotrophin nerve growth factor (NGF) is the best validated target in OA pain, with proven analgesic effects in preclinical and clinical studies, although the development of NGF-targeted therapeutics has been hampered by serious side effects. One relatively neglected area of research is the contribution to OA pain of the molecular pathways that mediate remodelling of nerves in disease. Remodelling requires coordination between the nerve and the associated vasculature, along with signals that are received from the surrounding parenchyma. Key cell guidance molecules, including angiogenic factors, ephrins, semaphorins and SLIT proteins are involved in nerve growth during development, and their expression is increased in osteoarthritic joints. Peripheral mechanisms of pain in osteoarthritis include nociceptor sensitization via the function of ion channels and pro-inflammatory molecules, and, potentially, pathways supporting neuronal growth and differentiation within the diseased joint. This Review discusses how neuronal trophism and neurovascular remodelling could be targeted in combination with neuronal de-sensitization or joint re-structuring approaches to reduce osteoarthritic pain.","PeriodicalId":18810,"journal":{"name":"Nature Reviews Rheumatology","volume":"21 9","pages":"526-545"},"PeriodicalIF":32.7,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144819225","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Parathyroid hormone receptor agonists in the management of osteoporosis","authors":"Nicholas Fuggle, René Rizzoli, Charlotte Beaudart, Bernard Cortet, Elizabeth M. Curtis, Mickaël Hiligsmann, Jean-Marc Kaufman, Nicola Veronese, Ben Hur Albergaria, Nasser Al-Daghri, Majed Alokail, Maria Luisa Brandi, Olivier Bruyère, Nansa Burlet, Claudia Campusano, Enrique Casado, Etienne Cavalier, Manju Chandran, Cyrus Cooper, Patrizia D’Amelio, Bess Dawson-Hughes, Peter R. Ebeling, John A. Kanis, Andreas Kurth, Radmila Matijevic, Eugene McCloskey, Michael McClung, Ouafa Mkinsi, Ngozi Njeze, Régis P. Radermecker, François Rannou, Stuart Silverman, Şansın Tüzün, Leith Zakraoui, Jean-Yves Reginster, Nicholas C. Harvey","doi":"10.1038/s41584-025-01287-w","DOIUrl":"10.1038/s41584-025-01287-w","url":null,"abstract":"Parathyroid hormone (PTH) regulates bone homeostasis. Intermittent exposure to PTH results in bone formation being greater than bone resorption, and this effect has been harnessed through the development of agonists of the PTH and PTH-related protein type 1 receptor (PTH1R) to treat osteoporosis. Teriparatide, an analogue of the first 34 amino acids of PTH, and abaloparatide, which resembles PTH-related protein (PTHrP) in structure, are PTH1R agonists currently in clinical use. Both medications have been shown to increase bone mineral density at the lumbar spine, femoral neck and total hip. Randomized controlled trials with teriparatide or abaloparatide have also provided evidence of reduction in vertebral and non-vertebral fractures. The ACTIVE trial suggested slightly greater efficacy for major osteoporotic fractures (as an exploratory end point) for abaloparatide than for teriparatide. A similar potential superiority was suggested for hip fracture in a real-world, observational study. Side effects of these medications are usually transient, and although a risk of osteosarcoma was suggested by studies using murine models, no such risk has been observed in extensive human studies. Overall, both teriparatide and abaloparatide have demonstrated convincing clinical effectiveness and cost-effectiveness, with a reassuring safety profile. Potential differences in their effects on bone mineral density and their antifracture effects offer avenues for differentiation but require further validation in appropriately designed studies. This Review summarizes clinical effectiveness, health economics and safety data on the parathyroid hormone receptor agonists teriparatide and abaloparatide, discussing potential strategies and drug combinations to achieve best outcomes in patients with osteoporosis.","PeriodicalId":18810,"journal":{"name":"Nature Reviews Rheumatology","volume":"21 10","pages":"599-611"},"PeriodicalIF":32.7,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144819226","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CD142+ synovial fibroblasts attack the meniscus in knee RA","authors":"Maria Papatriantafyllou","doi":"10.1038/s41584-025-01293-y","DOIUrl":"10.1038/s41584-025-01293-y","url":null,"abstract":"Meniscus damage caused by invasive CD142+ synovial fibroblasts seems to precede cartilage destruction in rheumatoid arthritis with severe knee involvement.","PeriodicalId":18810,"journal":{"name":"Nature Reviews Rheumatology","volume":"21 9","pages":"509-509"},"PeriodicalIF":32.7,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144796801","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"iPSC-derived CAR-NK cells for systemic sclerosis","authors":"Holly Webster","doi":"10.1038/s41584-025-01292-z","DOIUrl":"10.1038/s41584-025-01292-z","url":null,"abstract":"A chimeric antigen receptor (CAR)-natural killer (NK) cell therapy shows promise in a patient with severe systemic sclerosis and offers a scalable, off-the-shelf developmental approach.","PeriodicalId":18810,"journal":{"name":"Nature Reviews Rheumatology","volume":"21 9","pages":"509-509"},"PeriodicalIF":32.7,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144786623","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The apprehension of seronegative rheumatoid arthritis","authors":"Iqra Javed, Cynthia S. Crowson","doi":"10.1038/s41584-025-01289-8","DOIUrl":"10.1038/s41584-025-01289-8","url":null,"abstract":"Seronegative rheumatoid arthritis (RA) is often misunderstood and underrecognized, and this leads to delays in diagnosis and treatment. Emerging studies highlight distinct features and unmet needs of seronegative RA, calling for increased awareness of the challenges faced by patients and the need for tailored therapeutic approaches to improve outcomes.","PeriodicalId":18810,"journal":{"name":"Nature Reviews Rheumatology","volume":"21 10","pages":"575-576"},"PeriodicalIF":32.7,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144756460","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"More than a leaky gut: how gut priming shapes arthritis","authors":"Kristine A. Kuhn, Kentaro Yomogida, Kathryn Knoop, Hsin-Jung Joyce Wu, Mario M. Zaiss","doi":"10.1038/s41584-025-01282-1","DOIUrl":"10.1038/s41584-025-01282-1","url":null,"abstract":"The gut microbiome forms an ecosystem that provides the host with numerous benefits such as digestion with nutrient generation, protection from pathogens and immune system maturation. Alterations in the microbial ecosystem associated with rheumatoid arthritis and spondyloarthritis have led to the gut–joint hypothesis, which postulates that these ecological changes cause immune dysfunction that contributes to the development of arthritis. Mechanisms by which dysbiosis might trigger arthritis include molecular mimicry, dysregulation of mucosal immunity, microbial translocation, production of immunomodulatory metabolites and immune cell trafficking. We discuss the data supporting each of these mechanisms, and highlight misconceptions, limitations and gaps in knowledge. In particular, we advise against the term ‘leaky-gut’ as the mechanisms and effects on the immune system of intestinal permeability and bacterial translocation are distinct. Nevertheless, rheumatoid arthritis and spondyloarthritis possibly result from the convergence of multiple pathways that could be unique to subgroups of individuals within these diseases. To move the field forward, each mechanism needs to be considered through the use of model organisms and interventional trials, individually and in concert. This Review discusses how alterations in the gut are linked to the development of arthritis. The authors challenge the concept of the ‘leaky gut’ hypothesis, stating that the effects of intestinal permeability and bacterial translocation on the immune system are distinct.","PeriodicalId":18810,"journal":{"name":"Nature Reviews Rheumatology","volume":"21 9","pages":"513-525"},"PeriodicalIF":32.7,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144747292","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dynamic macrophage phenotypes in autoimmune and inflammatory rheumatic diseases","authors":"Maurizio Cutolo, Stefano Soldano, Vanessa Smith, Emanuele Gotelli, Elvis Hysa","doi":"10.1038/s41584-025-01279-w","DOIUrl":"10.1038/s41584-025-01279-w","url":null,"abstract":"Macrophages regulate inflammatory and fibrotic processes in several autoimmune and inflammatory rheumatic diseases. They are highly plastic cells, shifting within a range of pro-inflammatory and anti-inflammatory or pro-fibrotic phenotypes in response to dynamic interactions with other cells, environmental factors and cytokine signatures. The terms ‘M1 macrophages’, or classically activated, and ‘M2 macrophages’, or alternatively activated, were previously used to denote pro- and anti-inflammatory macrophage subsets, respectively, but this classification system has been outdated by in vivo evidence of a continuum of macrophage phenotypes that includes M1-like, M2-like and hybrid phenotypes. Deciphering the specific mechanisms that drive macrophage plasticity and function during the progression of rheumatoid arthritis, psoriatic arthritis, systemic sclerosis, systemic lupus erythematosus, and in synovitis and large vessel vasculitis in polymyalgia rheumatica and giant-cell arteritis, can improve our understanding of disease pathophysiology. Macrophage plasticity is enhanced in synovial tissue in rheumatoid arthritis, fibrotic skin and lung in systemic sclerosis, damaged kidney in systemic lupus erythematosus, and the bursal tissues or large vessels in polymyalgia rheumatica and giant-cell arteritis. Sophisticated transcriptomic analyses have revealed various phenotypic clusters of macrophages in biopsies of affected organs. Moreover, macrophage plasticity seems to be targeted by some standardized drugs used to treat the aforementioned conditions. Phenotypic and functional plasticity of macrophages is implicated in the pathophysiology of numerous autoimmune rheumatic diseases. In this Review, the authors discuss the latest insights into this complex and dynamic process and the potential implications for the treatment of these diseases.","PeriodicalId":18810,"journal":{"name":"Nature Reviews Rheumatology","volume":"21 9","pages":"546-565"},"PeriodicalIF":32.7,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144715325","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Timing matters in diagnosis of cancer with immune-mediated inflammatory disease","authors":"Dongxue Wang, Jianguang Ji","doi":"10.1038/s41584-025-01288-9","DOIUrl":"https://doi.org/10.1038/s41584-025-01288-9","url":null,"abstract":"Immune-mediated inflammatory diseases (IMIDs) are associated with cancer risk through mechanisms involving disrupted immune tolerance and dysregulated immune responses. Deng et al. investigated how the timing of IMID diagnosis relative to cancer diagnosis affects patient survival outcomes.","PeriodicalId":18810,"journal":{"name":"Nature Reviews Rheumatology","volume":"52 1","pages":""},"PeriodicalIF":33.7,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144694103","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Addressing the challenge of global delays in diagnosis and treatment of systemic lupus erythematosus","authors":"Guillermo J. Pons-Estel, María Fernanda Ramírez-Flores, Rosana Quintana, Sang-Cheol Bae, Dzifa Dey, Bernardo A. Pons-Estel, Ingris Peláez-Ballestas","doi":"10.1038/s41584-025-01277-y","DOIUrl":"10.1038/s41584-025-01277-y","url":null,"abstract":"Systemic lupus erythematosus is a complex and increasingly prevalent disease that presents substantial challenges in both diagnosis and management. Diagnostic delays frequently lead to irreversible organ damage, and remain a crucial concern, mainly among vulnerable populations, such as minority ethnic groups and those living in the global south. These delays are exacerbated by the clinical heterogeneity of systemic lupus erythematosus, the lack of specific diagnostic biomarkers, gaps in disease awareness or medical training, and persistent health care disparities, particularly in low-resource settings. This Perspective highlights the urgent need for a standardized definition of diagnostic delay that accounts for both clinical and socio-economic factors. By prioritizing early intervention and expanding access to specialized care, we can improve patient outcomes and reduce the long-term burden of the disease. Delays in the diagnosis of systemic lupus erythematosus negatively affect the treatment, quality of life and outcomes of affected individuals. In this Perspective, the authors provide an overview of the contributing factors and consequences of diagnostic delay in systemic lupus erythematosus and discuss how this urgent issue should be addressed.","PeriodicalId":18810,"journal":{"name":"Nature Reviews Rheumatology","volume":"21 9","pages":"566-574"},"PeriodicalIF":32.7,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144669630","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Guided management of familial Mediterranean fever","authors":"Hatem El-Shanti","doi":"10.1038/s41584-025-01281-2","DOIUrl":"10.1038/s41584-025-01281-2","url":null,"abstract":"Familial Mediterranean fever (FMF) is a monogenic autoinflammatory disorder with high prevalence in Mediterranean populations. Considerable advances in the management of FMF have been made in the past decade, with respect to the use of biologic drugs and understanding colchicine resistance. The 2024 updated FMF management recommendations are timely and reflect these advances.","PeriodicalId":18810,"journal":{"name":"Nature Reviews Rheumatology","volume":"21 10","pages":"578-579"},"PeriodicalIF":32.7,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144593920","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}