Inflammatory Diseases Causing Joint and Bone Destruction: Rheumatoid Arthritis and Hemophilic Arthropathy

Overview

Journal J Bone Miner Metab

Specialty Endocrinology

Date 2024 Jun 10

PMID 38856919

Authors

Asuka Terashima

Kumiko Ono

Yasunori Omata

Sakae Tanaka

Taku Saito

Affiliations

Soon will be listed here.

Abstract

Various diseases and conditions cause joint disorders. Osteoarthritis (OA) is characterized by the degeneration of articular cartilage, synovitis, and anabolic changes in surrounding bone tissues. In contrast, rheumatoid arthritis (RA) and hemophilic arthropathy (HA) display marked destruction of bone tissues caused by synovitis. RA is a representative autoimmune disease. The primary tissue of RA pathogenesis is the synovial membrane and involves various immune cells that produce catabolic cytokines and enzymes. Hemophilia is a genetic disorder caused by a deficiency in blood clotting factors. Recurrent intra-articular bleeding leads to chronic synovitis through excessive iron deposition and results in the destruction of affected joints. Although the triggers for these two joint diseases are completely different, many cytokines and enzymes are common in the pathogenesis of both RA and HA. This review focuses on the similarities between joint and bone destruction in RA and HA. The insights may be useful in developing better treatments for hemophilia patients with arthropathy and osteoporosis by leveraging advanced therapeutics for RA.

Citing Articles

Decision experiences in joint replacement surgery for patients with haemophilic arthritis: A qualitative study.

Kan Y, Bao Y, Ye F BMC Med Inform Decis Mak. 2025; 25(1):55.

PMID: 39905363 PMC: 11792258. DOI: 10.1186/s12911-025-02901-3.

References

Schonbeck U, Mach F, Libby P . Generation of biologically active IL-1 beta by matrix metalloproteinases: a novel caspase-1-independent pathway of IL-1 beta processing. J Immunol. 1998; 161(7):3340-6. View

Kojima M, Nakayama T, Tsutani K, Igarashi A, Kojima T, Suzuki S . Epidemiological characteristics of rheumatoid arthritis in Japan: Prevalence estimates using a nationwide population-based questionnaire survey. Mod Rheumatol. 2019; 30(6):941-947. DOI: 10.1080/14397595.2019.1682776. View

Melchiorre D, Morfini M, Linari S, Zignego A, Innocenti M, Cerinic M . Anti-TNF-α therapy prevents the recurrence of joint bleeding in haemophilia and arthritis. Rheumatology (Oxford). 2013; 53(3):576-8. DOI: 10.1093/rheumatology/ket280. View

Kalluri R . The biology and function of fibroblasts in cancer. Nat Rev Cancer. 2016; 16(9):582-98. DOI: 10.1038/nrc.2016.73. View

Calvez T, Chambost H, Claeyssens-Donadel S, dOiron R, Goulet V, Guillet B . Recombinant factor VIII products and inhibitor development in previously untreated boys with severe hemophilia A. Blood. 2014; 124(23):3398-408. DOI: 10.1182/blood-2014-07-586347. View

Green M, Gough A, Devlin J, Smith J, Astin P, Taylor D . Serum MMP-3 and MMP-1 and progression of joint damage in early rheumatoid arthritis. Rheumatology (Oxford). 2003; 42(1):83-8. DOI: 10.1093/rheumatology/keg037. View

Kulkarni R, Soucie J . Pediatric hemophilia: a review. Semin Thromb Hemost. 2011; 37(7):737-44. DOI: 10.1055/s-0031-1297164. View

Narazaki M, Tanaka T, Kishimoto T . The role and therapeutic targeting of IL-6 in rheumatoid arthritis. Expert Rev Clin Immunol. 2017; 13(6):535-551. DOI: 10.1080/1744666X.2017.1295850. View

Narkbunnam N, Sun J, Hu G, Lin F, Bateman T, Mihara M . IL-6 receptor antagonist as adjunctive therapy with clotting factor replacement to protect against bleeding-induced arthropathy in hemophilia. J Thromb Haemost. 2013; 11(5):881-93. PMC: 3656980. DOI: 10.1111/jth.12176. View

10.

Matsuo K, Owens J, Tonko M, Elliott C, Chambers T, Wagner E . Fosl1 is a transcriptional target of c-Fos during osteoclast differentiation. Nat Genet. 2000; 24(2):184-7. DOI: 10.1038/72855. View

11.

Stahl E, Raychaudhuri S, Remmers E, Xie G, Eyre S, Thomson B . Genome-wide association study meta-analysis identifies seven new rheumatoid arthritis risk loci. Nat Genet. 2010; 42(6):508-14. PMC: 4243840. DOI: 10.1038/ng.582. View

12.

Haxaire C, Hakobyan N, Pannellini T, Carballo C, McIlwain D, Mak T . Blood-induced bone loss in murine hemophilic arthropathy is prevented by blocking the iRhom2/ADAM17/TNF-α pathway. Blood. 2018; 132(10):1064-1074. PMC: 6128089. DOI: 10.1182/blood-2017-12-820571. View

13.

Redlich K, Hayer S, Ricci R, David J, Tohidast-Akrad M, Kollias G . Osteoclasts are essential for TNF-alpha-mediated joint destruction. J Clin Invest. 2002; 110(10):1419-27. PMC: 151809. DOI: 10.1172/JCI15582. View

14.

Iwamoto T, Okamoto H, Toyama Y, Momohara S . Molecular aspects of rheumatoid arthritis: chemokines in the joints of patients. FEBS J. 2008; 275(18):4448-55. DOI: 10.1111/j.1742-4658.2008.06580.x. View

15.

Ovlisen K, Kristensen A, Jensen A, Tranholm M . IL-1 beta, IL-6, KC and MCP-1 are elevated in synovial fluid from haemophilic mice with experimentally induced haemarthrosis. Haemophilia. 2009; 15(3):802-10. DOI: 10.1111/j.1365-2516.2008.01973.x. View

16.

Eyre S, Bowes J, Diogo D, Lee A, Barton A, Martin P . High-density genetic mapping identifies new susceptibility loci for rheumatoid arthritis. Nat Genet. 2012; 44(12):1336-40. PMC: 3605761. DOI: 10.1038/ng.2462. View

17.

McInnes I, Schett G . Cytokines in the pathogenesis of rheumatoid arthritis. Nat Rev Immunol. 2007; 7(6):429-42. DOI: 10.1038/nri2094. View

18.

Lindy O, Konttinen Y, Sorsa T, Ding Y, Santavirta S, Ceponis A . Matrix metalloproteinase 13 (collagenase 3) in human rheumatoid synovium. Arthritis Rheum. 1997; 40(8):1391-9. DOI: 10.1002/art.1780400806. View

19.

Safiri S, Kolahi A, Hoy D, Smith E, Bettampadi D, Mansournia M . Global, regional and national burden of rheumatoid arthritis 1990-2017: a systematic analysis of the Global Burden of Disease study 2017. Ann Rheum Dis. 2019; 78(11):1463-1471. DOI: 10.1136/annrheumdis-2019-215920. View

20.

Kochi Y, Okada Y, Suzuki A, Ikari K, Terao C, Takahashi A . A regulatory variant in CCR6 is associated with rheumatoid arthritis susceptibility. Nat Genet. 2010; 42(6):515-9. DOI: 10.1038/ng.583. View