Authors
Kokorin V.V. 1, 3, Deev R.V.2, Kraynyukov P.E.1, 4, Matveev S.A.3
1 P.V. Mandryka Central Military Clinical Hospital, Moscow
2 A.P. Avtsyn Research Institute of Human Morphology, Petrovsky National Research Centre of Surgery, Moscow
3 Pirogov National Medical and Surgical Center, Moscow
4 RUDN University, Moscow
Abstract
Periarticular tissues have traditionally been regarded as a collection of discrete peri-articular structures surrounding the joint – tendons, ligaments, joint capsule, fasciae, synovial bursae, entheses and muscles. Emerging evidence indicates that in chronic pathology these structures function as a unified neurovascular–connective tissue “organ”, in which mechanical injury, disturbed innervation, impaired vascular regulation and persistent inflammation, including infection-associated inflammation, converge into a common pathogenetic trajectory leading to enthesopathy. This review summarizes current data on the structure and pathophysiology of periarticular tissues, the role of the peripheral nervous system and the microvascular bed, as well as the contribution of infectious triggers to the development of the pathological process. We discuss the concept of a pathogenetic cascade: “mechanical loading – neural dysregulation – vascular remodelling and pathological angiogenesis – infection-driven and autoimmune inflammation – chronicity and structural remodelling of the enthesis organ”. Particular attention is paid to clinical and imaging features of lesions of the synovio-entheseal complex and their relationship to cellular, structural and metabolic disturbances. Potential therapeutic targets in enthesopathy are outlined, including modulation of angiogenesis, neurovascular complexes and immune pathways. The proposed model provides a framework for unifying approaches to diagnosis and treatment of periarticular pathology.
Keywords: periarticular tissues; enthesis; enthesopathy; synovio-entheseal complex; angiogenesis; peripheral nervous system; infection; IL-23/IL-17.
References
1. Iordan DA, Leonard S, Matei DV, et al. Understanding Scapulohumeral Periarthritis: A Comprehensive Systematic Review. Life. 2025; 15(2): 186. doi: 10.3390/life15020186.
2. Zhilyakov AA, Kokorina ML, Zerchaninova EI. Entezis kak organ i ego patologii. Bulletin of the Ural Medical Academic Science. 2022; 19(5): 433-442. (In Russ.) doi: 10.22138/ 2500-0918-2022-19-5-433-442.
3. Abdulgantieva DI, Kirillova ER, Fairushina IF, et al. Entezopatii pri spondiloartritakh: obzor literatury. Rheumatology Science and Practice. 2021; 59(3): 316-325. (In Russ.)
4. Devald IV, Khodus EA, Belsner MS, Minakina OL. Differentsialnyy diagnoz i lechenie entezoapatiy. Medical Council. 2024; 18(3): 159-166. (In Russ.)
5. Sabido-Sauri R, Baraliakos X, Aydın SZ. Enthesopathies – mechanical, inflammatory or both? Best Pract Res Clin Rheumatol. 2024; 38(1): 101966. doi: 10.1016/j.berh.2024.101966.
6. Yıldız AE, Aydıngöz Ü. Pivotal role of the synovioentheseal complex in the imaging of arthritis and rheumatic diseases. Diagn Interv Radiol. 2024; 30(6): 409-418. doi: 10.4274/dir.2024.242740.
7. Russell T, Bridgewood C, Rowe H, et al. Cytokine “fine tuning” of enthesis tissue homeostasis as a pointer to spondyloarthritis pathogenesis with a focus on relevant TNF and IL-17 targeted therapies. Semin Immunopathol. 2021; 43(2): 193-206. doi: 10.1007/s00281-021-00836-1.
8. Gehwolf R, Tempfer H, Cesur NP, Wagner A, Traweger A, Lehner C. Tendinopathy: The Interplay between Mechanical Stress, Inflammation, and Vascularity. Adv Sci. 2025; 12(36): e06440. doi: 10.1002/advs.202506440.
9. Tempfer H, Traweger A. Vascular dynamics in tendon health and pathology: exploring mechanisms and therapeutic opportunities. Eur Cells Mater. 2025; 53: 65-81. doi: 10.22203/eCM.v053a06.
10. Shahid H, Morya VK, Oh J-U, Kim J-H, Noh K-C. Hypoxia-Inducible Factor and Oxidative Stress in Tendon Degeneration: A Molecular Perspective. Antioxidants. 2024; 13(1): 86. doi: 10.3390/antiox13010086.
11. Szwedowski D, Ciszek B, Gagat M, et al. Neovascularization in meniscus and tendon pathology as a potential mechanism in regenerative therapies: Special reference to platelet-rich plasma treatment. Appl Sci. 2021; 11(18): 8310.
12. Mandour M, Eltorai AEM, Ibrahim S, et al. The role of the IL-23/IL-17 axis in disease initiation in spondyloarthritis. Front Immunol. 2021; 12: 618581.
13. Lisco G, De Tullio A, Zupo R, et al. Metabolic-associated enthesitis: A review on pathophysiology, clinical relevance, diagnostic challenges, and perspective on target treatments. Immunol Res. 2025; 73(1). (Epub ahead of print).
14. Nakamichi R, Asahara H. Regulation of tendon and ligament differentiation. Bone. 2021; 143: 115609. doi: 10.1016/j.bone.2020.115609.
15. Darrieutort-Laffite C, Blanchard F, Soslowsky LJ, Le Goff B. Biology and physiology of tendon healing. Joint Bone Spine. 2024; 91(5): 105696. doi: 10.1016/j.jbspin.2024.105696.
16. Dydykina IS, Arutyunova EV, Kovalenko PS, et al. Sinovit pri osteoartrite: sovremennoe sostoyanie problemy. Modern Rheumatology Journal. 2021; 15(2): 120-125. (In Russ.) doi: 10.14412/1996-7012-2021-2-120-125.
17. Di Matteo A, Smerilli G, Di Donato S, et al. Power Doppler signal at the enthesis and bone erosions are the most discriminative OMERACT ultrasound lesions for SpA: Results from the DEUS multicentre study. Ann Rheum Dis. 2024; 83(7): 847-857.
18. Rajpar I, Barrett M, Lawson MA, et al. Function of peripheral nerves in the development and healing of tendon and bone. Semin Cell Dev Biol. 2022; 123: 48-56. doi: 10.1016/j.semcdb.2021.05.001.
19. Hassan MG, Horenberg AL, Coler-Reilly A, et al. Role of the peripheral nervous system in skeletal development and regeneration: controversies and clinical implications. Curr Osteoporos Rep. 2023; 21(6): 503-518. doi:10.1007/s11914-023-00815-5.
20. Kong L, Gao X, Qian Y, et al. Biomechanical microenvironment in peripheral nerve regeneration: from pathophysiological understanding to tissue engineering development. Theranostics. 2022; 12(11): 4993-5014. doi: 10.7150/thno.74571.
21. Saito T, Nakamichi R, Yoshida A, et al. The effect of mechanical stress on enthesis homeostasis in a rat Achilles enthesis organ culture model. J Orthop Res. 2022; 40(8): 1872-1882.
22. Kokorin VV, Krainyukov PE. Rezul’taty eksperimental’nogo issledovaniya strukturnykh izmeneniy soedinitel’noy tkani pri khronicheskoy khirurgicheskoy patologii ishemicheskogo geneza: rol’ angiogeneza. Bulletin of N.I. Pirogov National Medical and Surgical Center. 2023; 18(2): 21-28. (In Russ.)
23. Rhim HC, Kim MS, Choi S, et al. A systematic review of systematic reviews on the epidemiology, diagnosis, and treatment of plantar fasciitis. Orthop J Sports Med. 2021; 9(12): 23259671211044020. doi: 10.1177/23259671211044020.
24. Fine AM, Vlasov AP, Akimov RN, et al. Lechenie povrezhdeniya akhillova suhozhiliya. Istoriya i sovremennoe sostoyanie problemy. Journal named after N.V. Sklifosovsky “Emergency Medical Care”. 2022; 11(4): 655-667. (In Russ.) doi: 10.23934/ 2223-9022-2022-11-4-655-667.
25. Bruni DF, Tetreault MW, Monib A, et al. Are the pathologic features of enthesopathy, tendinopathy, and labral and articular disc disease related to mucoid degeneration? A systematic review. Clin Orthop Relat Res. 2023; 481(11): 2077-2095.
26. Cordeiro TTP, Patricio Cordeiro T, Oliveira JR, et al. Effects of exercise-based interventions on gluteal tendinopathy: a systematic review and meta-analysis. Sci Rep. 2024; 14: 53283.
27. Kokorin VV. Eksperimental’noe obosnovanie etiopatogeneticheskogo podkhoda v khirurgii patologii periartikuljarnykh tkanei. Bulletin of N.I. Pirogov National Medical and Surgical Center. 2022; 17(2): 43-48. (In Russ.)
28. Seidman AJ, Limaiem F. Synovial Fluid Analysis. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan.
29. Damasco AC, Moraes JCB, Azevedo MN, et al. Physiopathological aspects of synovial fluid and relevance in inflammatory arthritis. Rheumato. 2024; 4(4): 15. doi: 10.3390/rheumato4040015.
30. Shevchenko YuL, Krainyukov PE, Kokorin VV. Izuchenie roli angiogeneza v regulyatsii strukturnykh izmeneniy soedinitel’noy tkani pri khronicheskoy khirurgicheskoy patologii ishemicheskogo geneza v eksperimente. Bulletin of N.I. Pirogov National Medical and Surgical Center. 2023; 18(1): 14-19. (In Russ.)
31. Shevchenko YuL. Immobiliziruyushchiy interstitsial’nyy fibroz serdtsa. Bulletin of N.I. Pirogov National Medical and Surgical Center. 2022; 17(2): 4-10. (In Russ.)
32. Shevchenko YuL, Matveev SA, Pinaev GP, et al. Eksperimental’noe obosnovanie vozmozhnosti implantatsii embrional’nykh kardiomiotsitov v kompleksnoy terapii miokardial’noy slabosti. Human Physiology. 1999; 25(4): 109-117. (In Russ.)
33. Golovach IYu. Clinical significance of spondyloarthritis-attended enthesites: from pathophysiology to treatment (review). Pain Joints Spine. 2021; 11(1): 17-27. doi: 10.22141/2224-1507.11.1.2021.226905.
