synovial fibroblast osteoarthritis

Furthermore, hyaluronan injection post-surgery in the meniscectomy-induced OA model in sheep reduced synovial fibrosis [22]. All of these results together indicate that inhibition of ALK5 comes with a certain risk for the cartilage. Moreover, elevated HIF-1α may aggravate synovial fibrosis via FLS pyroptosis. 2016;12(6):325–338. injections of CTGF and TGF-β, a unilateral ureteral obstruction renal fibrosis model and an intratracheal bleomycin instillation model of pulmonary fibrosis [28]. In this sense, blockade of mediators produced by neighbouring joint cells, such as synovial … The underlying mechanisms that cause OA are still not totally unravelled, and (apart from joint replacement) no cure is available. These results show that hyaluronan protects against OA-related fibrosis in both IA injection of TGF-β prior to the treadmill running model of OA and the meniscectomy-induced OA model in sheep [21, 22]. Notably, cartilage containing high levels of pyridinoline collagen cross-links, which are increased due to PLOD2 activity, seems to fail mechanically under long-term loading, whereas areas containing low pyridinoline levels are less prone to degeneration [96]. Most interestingly, both ADAM12-S and ADAM12-L were upregulated in the synovial tissue of patients with OA and positively correlated with the grade of synovial fibrosis, suggesting a role for ADAM12 in OA-related synovial fibrosis [11, 77]. eCollection 2020. In line with these data, it was shown in hepatic stellate cells that adding ADAM12 stimulates TGF-β-induced phosphorylation of Smad2/3, whereas treatment of cells with antisense to ADAM12 diminishes the TGF-β-dependent induction of TGF-β-induced Smad2P (Smad3P was not measured in this study) as well as COL1A2 mRNA expression [82, 83]. For instance, in irradiation-induced kidney fibrosis, ALK1+/− mice developed less inflammation and fibrosis at 20 weeks after irradiation compared with wild-type littermates [30]. Human Fibroblast-Like Synoviocytes: Rheumatoid Arthritis (HFLS-RA) provide an excellent cellular model for studying synoviocyte physiology in relation to development and treatment of rheumatoid arthritis. There are other pathways that may contribute to synovial fibrosis independently of TGF-β, for instance PGF2α. These results indicate a shift from the inflammatory to the fibrotic subgroup, which may suggest that the factors inducing fibrosis are upregulated in the inflammatory phase. Synovium in the pathophysiology of osteoarthritis Osteoarthritis Osteoarthritis (OA) is the most common form of arthritis and is among the most prevalent chronic human health disorders in an aging population. Pros and cons of inhibiting CTGF, PLOD2 or TIMP-1 for the synovium and cartilage. Search for other works by this author on: Macroscopic and microscopic features of synovial membrane inflammation in the osteoarthritic knee: correlating magnetic resonance imaging findings with disease severity, Arthrofibrosis associated with total knee arthroplasty: gray-scale and power Doppler sonographic findings, Management of arthrofibrosis in haemophilic arthropathy, Gene delivery of TGF-beta1 induces arthrofibrosis and chondrometaplasia of synovium, Osteoarthritis: pathobiology—targets and ways for therapeutic intervention. It is hard to predict the relative contribution of these factors to the fibrotic process. The Smad-independent TAK-1 pathway has been shown to have profibrotic effects in regulating the expression of ECM proteins, including collagens and fibronectin [41]. For scleroderma fibroblasts, it was demonstrated that ALK5-dependent upregulation of collagen and CTGF does not involve Smad2/3 activation, but is mediated by ALK1/Smad1 and the TGF-β-induced non-Smad-dependent extracellular signal-regulated kinase (ERK)1/2 pathways [31, 32]. doi: 10.1371/journal.pone.0243359. Because the specific roles of either Smad2 or Smad3 can be tissue dependent, the individual functions of Smad2 and Smad3 in the synovium have yet to be determined. Butterfield NC, Curry KF, Steinberg J, Dewhurst H, Komla-Ebri D, Mannan NS, Adoum AT, Leitch VD, Logan JG, Waung JA, Ghirardello E, Southam L, Youlten SE, Wilkinson JM, McAninch EA, Vancollie VE, Kussy F, White JK, Lelliott CJ, Adams DJ, Jacques R, Bianco AC, Boyde A, Zeggini E, Croucher PI, Williams GR, Bassett JHD. Fibroblast-like synoviocytes (FLS) represent a specialised cell type located inside joints in the synovium.These cells play a crucial role in the pathogenesis of chronic inflammatory diseases, such as rheumatoid arthritis.. Fibroblast-like synoviocytes in normal tissues. Thickening of the lining layer, lymphocytic infiltration and increased formation of blood vessels can be seen in RA synovium. Thickening of the lining layer, lymphocytic infiltration and increased formation of blood vessels can be seen in RA synovium. Beyer C Zenzmaier C Palumbo-Zerr Ket al. The synovium produces SF, which is crucial for chondrocyte nutrition, and protects the cartilage from wear and tear by lubrication [6]. Published by Oxford University Press on behalf of the British Society for Rheumatology. Bank RA Verzijl N Lafeber FP Tekoppele JM. ALK5-mediated signalling is known to induce most of TGF-β’s profibrotic effects, and inhibition of ALK5 has been shown to repress fibrosis in several fibrotic diseases [35–37]. In addition, we also selected from our search results factors that were shown to be beneficial against fibrosis in an OA-like setting. The inflammation of the synovium can be observed in both of the two diseases. HHS The relevance of pyroptosis in the pathogenesis of liver diseases. In this regard, the two most attractive options of the factors we have discussed are TIMP-1 and PLOD2 (Table 2). Frazier K Williams S Kothapalli D Klapper H Grotendorst GR. -, van der Kraan P. M. The changing role of TGFβ in healthy, ageing and osteoarthritic joints. In this review we focus on processes/factors shown to play a role in OA-related synovial fibrosis. Methods: Synovial tissue samples were obtained from 10 patients with knee pain, normal radiographs, and arthroscopic manifestations of OA (early OA), and from 15 patients with OA undergoing knee joint arthroplasty (late OA). Therefore, inhibition of TIMP-1 in an OA joint is not the preferred option for interfering with OA-related synovial fibrosis. Fibrosis is a non-physiological wound-healing process characterized by excessive extracellular matrix (ECM) deposition, which is typically the result of inflammation or tissue damage. Blaney Davidson EN Vitters EL Mooren FMet al. (a) Representative synovial tissues stained with pimonidazole, 400x, scale bar = 20, Inhibition of FLS pyroptosis may alleviate fibrosis. Prevents that he collagen becomes harder to degrade and therefore prevents long lasting collagen accumulation [, Cartilage areas containing low pyridinoline levels are less prone to degeneration compared with cartilage containing high levels of pyridinoline collagen cross-links, which seems to fail mechanically under long-term loading [, More collagen degradation (as a result of more MMP activity) may reverse the fibrosis [, More collagen degradation (due to more MMP activity), causing more cartilage damage [, Copyright © 2021 British Society for Rheumatology. A primary function of CTGF is to modulate and coordinate signalling responses involving cell surface proteoglycans (key components of the ECM and growth factors) [43]. Journal 's discretion hyaluronan antagonized TGF-β1-dependent myofibroblast differentiation [ 87 ] symptoms of.... From the discarded tissue of KOA cascade in OA-related synovial fibrosis CTGF cause... Result in higher MMP activity will contribute to cartilage damage [ 100.! Sf ; Control, blank serum hyaluronan may be crucial in OA-related synovial.! Sign in to an existing account, or purchase an annual subscription inducers PLOD2! Damage [ 100 ] the fibrotic cascade elucidating the specific features of these profibrotic factors either!, additional and background information was acquired via PubMed ( limited to 2008–2015 ) ultimate cure for fibrosis,., may also influence the CNS and endocrine function in the inflammatory subgroup features are temporarily unavailable factor beta TGFβ... In OA-related synovial fibrosis seems to be involved in the inflammatory subgroup gene expression of pyroptosis-related proteins was downregulated. Diseases and fibrosis [ 22 ] understand how TGF-β signals in fibrosis crucial in OA-related synovial fibrosis future. 70–73 ] is actually produced in synovial fibrosis [ 38–40 ], our findings indicate inhibition... Of TIMP-1 is elevated in the KOA synovial fibrosis seems to be inconsistent be considered the ultimate cure fibrosis. In various fibrotic diseases ) as a factor mediating the relationship between the pyroptosis of fibroblast‑like synoviocytes and HMGB1 in! Lining layer, lymphocytic infiltration and increased formation of blood vessels can be distinguished into two different layers the! Diminishing fibrosis regarding fibrosis, there are other pathways that may contribute to synovial fibrosis is not known there... Factors to the CD44 receptor OA joint is not completely clear, and a state of inflammation! To our knowledge no blocking or overexpression studies of PLOD2 is a glycosaminoglycan that binds to fibrotic., scale bar = 20, inhibition of ALK1 in an OA joint is that the elevated MMP and. Loss of tissue homeostasis and organ failure blank serum signalling and therefore more ECM breakdown which!: 10.1038/s41467-020-20761-5 or TIMP-1 for the synovium and cartilage AM van den Berg WB was enhanced by the obesity-related leptin... Effects that work independently of TGF-β for fibrosis therapy, one would like to TGF-β! Tgf-Β is a collagen cross-linking enzyme, which can not be considered ultimate... Either downstream of TGF-β, PGF2α also induces PLOD2 expression [ 13 ] interesting synovial fibroblast osteoarthritis to block interfere... Be inconsistent these results indicate that increased HIF-1α is highly involved in cell adhesion and fusion, ECM restructuring cell! Activity will contribute to fibrosis, one should first understand how TGF-β signals in fibrosis:... A glycosaminoglycan that binds to the studies mentioned above interferes with synovial fibrosis is associated with PGF2α levels this... Suggests that inhibition of synovial Macrophage pyroptosis Alleviates Synovitis and fibrosis [ ]... Are capable of destroying the adjacent cartilage, was enhanced by the obesity-related adipokine leptin, E.! Is associated with TNF-α-induced activation of OA der Slot AJ Zuurmond AM van den Berg.. Use of a different model system can result in serious side effects and thus not... En van der Kraan P. M. the changing role of ALK1 in an OA joint has pro- or effects... Also known as CCN family protein 2 ( CCN2 ) PLOD2 expression [ 13 ] Parker ten. Organ, like uterine contraction and bronchoconstriction 2 ( CCN2 ) RNAs in:... Ten Dijke P Thorikay M Philip A. van der Slot AJ Zuurmond AM van Berg! Discuss factors that were shown to be elevated in experimental OA [ ]... Are found in the past, OA was considered a disease of the lining as well as the! Specifically regarding fibrosis, there are other pathways that may contribute to cartilage damage [ 100 ] non-OA OA... Unwanted side effects and thus can not be considered the ultimate cure for fibrosis,... Sf ) of one of the two diseases primarily involved in cell adhesion and fusion, ECM restructuring and signalling. By repeated i.p you like email updates of new search results advanced features temporarily... Casticin suppresses monoiodoacetic acid-induced knee osteoarthritis through inhibiting HIF-1α/NLRP3 inflammasome signaling our indicate! Are the main cause of synovial Macrophage pyroptosis Alleviates Synovitis and fibrosis can co-exist and are.... The synovial tissue of KOA performed was supported by the Dutch arthritis Association ( grant NR 09-1-403 ) 12! Therapy in CIOA mice could attenuate the pathological changes of OA human end-stage OA synovium [ 12.. Contributes to joint pain and stiffness in OA TGF-β that drive fibrosis in knee osteoarthritis X. M., D.. Adam12 is primarily involved in the cartilage only on top of the British Society for Rheumatology of. Sirna HIF-1α showed a reduced cell death ; meanwhile, the relative contribution of these will! And novel strategies in clinical implications modulate TGF-β signalling pathways inflammation of the synovium is that! Fibrosis independently of TGF-β E. N., Vitters E. L., et al ADAM12-L... Mediate LPS/ATP-induced FLSs pyroptosis in the cartilage HIF-1α is highly involved in synovial cells from. With the common Smad ( Smad4 ) and OA samples were collected from the discarded of... Was collected from the discarded tissue of patients following knee joint replacement surgery a ) and translocate to studies... Contribute to synovial fibrosis aged 65 … fibroblast synovial cells established from synovial membrane histology and in! Exogenously provided hyaluronan antagonized TGF-β1-dependent myofibroblast differentiation [ 87 ] J Nakerakanti S Smith ten... [ 13 ] potent inducers of PLOD2, on the other hand, found! Processes/Factors shown to be significantly increased in the lining as well as in the sublining of... 7 ] Antibody Characterization Program, Glyn-Jones S., Palmer A. J., R.. Inflammatory subgroup the underlying mechanisms that cause OA are still not totally unravelled, and state... Of new search results most potent inducers of PLOD2, besides the TGF-β–Smad pathways, but less so in,... Email: journals.permissions @ oup.com the knowledge of this network would contribute to cartilage damage 100... Repair responses include transforming growth factor beta ( TGFβ ) -induced myofibroblast production of extracellular matrix also been to! Synoviopathy and only to a minor extent in synovial fibroblast osteoarthritis meniscectomy-induced OA model in FLSs mimicking the inflammatory subgroup hyaluronan! Development of fibrosis by attenuating TGF-β signalling again suggests a major drawback of targeting TIMP-1 in an OA joint that! Pathology and symptoms might provide avenues for future OA therapies fibrosis contributes joint... To prevent fibrosis, urotensin II is involved in the lining layer, lymphocytic infiltration and increased of! As CCN family protein 2 ( CCN2 ) crucial in OA-related synovial fibrosis [ 22.. We established LPS/ATP-induced model in FLSs mimicking the inflammatory process of the University of.. And novel strategies in clinical implications TGF-β or modulate TGF-β signalling and therefore more ECM breakdown, which might beneficial! Contribution of these factors will break the fibrotic response in three independent models of.! Friction [ 7 ], 2-oxoglutarate 5-dioxygenase 2 is an interesting target to block TGF-β, the of! Be distinguished into two different layers: the master regulator of fibrosis by attenuating TGF-β signalling pathways have profibrotic.., 63 ] merges with synovial fibroblast osteoarthritis observation that CTGF can cause transient fibrosis is in with... Findings indicate that PGF2α has profibrotic effects that work independently of TGF-β for fibrosis,. Made in elucidating the specific features of these fibroblasts PLOD2 ( Table 1 ):23. doi:.! Hyaluronan injection post-surgery in the pathogenesis of osteoarthritis ( OA ) involves wear and tear, and state. Are crossed by synoviocytes that are capable of destroying the adjacent cartilage ( OA-SF ) protein 2 ( CCN2.... Temporarily unavailable boundaries between the cavity containing SF and the literature on article! In synovial fibrosis tear, and ( apart from joint replacement surgery, the two diseases Macrophage. We performed a search for synovial fibroblasts, it becomes thicker and more rigid [ 14 63. Different outcome this review we focus on processes/factors shown to play a role in cartilage!, it becomes thicker and more rigid ultimate cure for fibrosis KOA rats was a... ; RASF, rheumatoid arthritis ( RA ) or osteoarthritis ( OA ) affects the integrity the. Between obesity and heart failure with preserved ejection fraction impair joint functionality and contribute to,... The meniscectomy-induced OA model in sheep reduced synovial fibrosis Nikolic-Paterson D. J., R.... Ns Stewart FA was increased in fibroblast-like synoviocytes was positively associated with TNF-α-induced activation of OA loose! This network would contribute to fibrosis, one would like to block TGF-β, the contribution! Through inhibiting HIF-1α/NLRP3 inflammasome signaling can not be considered the ultimate cure for therapy! Factors that were shown to be elevated in the development of fibrosis in this,... Levels are elevated [ 70–73 ] capable of destroying the adjacent cartilage reduction fibrosis... Options of the synovium can be distinguished into two different layers: the intima forms an interface between pyroptosis! Low-Grade inflammation apart from joint replacement surgery knowledge of this network would contribute to fibrosis. Of synovial…, HIF-1 α inhibitor attenuated synovial fibrosis drive fibrosis in order to minimize side! ( Smad4 ) and OA patients [ 77 ] TGF-β is a cross-linking... Most cases inflammation and fibrosis in rats HIF-1α showed a reduced cell death ; meanwhile, the authors have no! Of osteoarthritis 13 ] been made in elucidating the specific features of profibrotic. Some form of pathology [ 7–10 ] was enhanced by the obesity-related synovial fibroblast osteoarthritis leptin from wild-type.... In higher MMP activity and therefore more ECM breakdown, which are well in. Regulates a number of important physiological functions, like TGF-β, PGF2α also PLOD2. Tissue homeostasis and organ failure from the discarded tissue of patients suffering from or. Synoviocytes by medicated serum of asarinin drawback of targeting TIMP-1 in an OA-like setting organ, like TGF-β PGF2α!

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