IL-37 diminishes proteoglycan loss in human OA cartilage: donor-specific link between IL-37 and MMP-3

Geffen, E.W. van; Caam, A. van; Schreurs, Wim; Loo, F.A. van de; Lent, P.L.E.M. van; Koenders, Marije I.; Thudium, Christian S.; Bay‐Jensen, Anne‐Christine; Davidson, E.N. Blaney; Kraan, P.M. van der

doi:10.1016/j.joca.2018.08.016

Cited by 14 publications

(11 citation statements)

References 41 publications

(36 reference statements)

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“…Therefore, inhibiting the expression levels of MMP-13 may lead to cartilage protection and therefore have therapeutic value in the treatment of OA (25,26). MMP-3 has also been discovered to be closely associated with the progression of OA and increased MMP-3 expression levels have been observed to promote collagen degradation in the cartilage matrix (27). In a previous study, the abnormal expression levels of MMP-3 were related to the pathogenesis of OA (28).…”

Section: Discussionmentioning

confidence: 97%

Vitamin D3 protects articular cartilage by inhibiting the Wnt/β‑catenin signaling pathway

Yang¹,

Sun

Duan³

et al. 2020

Exp Ther Med

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Low expression levels of 25-hydroxyvitamin D (vitamin D3) in the blood have been reported to be associated with the progression of osteoarthritis; however, the mechanisms by which this occurs remain unclear. The present study aimed to determine the effects of vitamin D3 on chondrocytes. MTT assays were used to determine whether vitamin D3 affects chondrocytes viability. Primary chondrocytes were treated with control culture medium, vitamin D3, tumor necrosis factor (TNF)-α, TNF-α + PNU-74654 [Wingless-related integration site (Wnt)/β-catenin signaling pathway inhibitor] or TNF-α + vitamin D3. Reverse transcription-quantitative PCR and western blotting were utilized to measure the gene and protein expression of collagen II, aggrecan, matrix metalloproteinase (MMP)-3 and MMP-13, A disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)-4, ADAMTS-5, Wnt-3a and nuclear β-catenin. The results demonstrated that TNF-α reduced the expression levels of aggrecan and collagen II, and increased the expression levels of MMP-3, MMP-13, ADAMTS-4 and ADAMTS-5. Furthermore, vitamin D3 and PNU-74654 were observed to partially attenuate the effects induced by TNF-α. Moreover, similar findings were reported following co-treatment with vitamin D3 and TNF-α. Western blotting data revealed that TNF-α increased Wnt-3a and β-catenin protein levels in chondrocytes, while Vitamin D3 and PNU-74654 decreased the expression levels of Wnt-3a and nuclear β-catenin. In conclusion, the findings of the present study provided evidence to suggest that vitamin D3 may prevent articular cartilage degeneration and osteoarthritic disease progression by inhibiting the expression levels of MMP-3, MMP-13, ADAMTS-4 and ADAMTS-5 through suppressing the Wnt/β-catenin signaling pathway. These results suggested that vitamin D3 may be of therapeutic value for the prevention and treatment of osteoarthritis.

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Section: Discussionmentioning

confidence: 97%

Vitamin D3 protects articular cartilage by inhibiting the Wnt/β‑catenin signaling pathway

Yang¹,

Sun

Duan³

et al. 2020

Exp Ther Med

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“…However, a hallmark of OA, is cartilage proteoglycan degradation mediated by MMPs and ADAMTSs. Expressions of MMPs and ADAMTSs are both elevated in OA cartilage and activities of both MMPs and ADAMTSs are positively associated with cartilage degradation (29,30). Matrix-degrading enzymes secreted by chondrocytes (e.g., MMPs and ADAMTSs) degrade the extracellular matrix (ECM) of cartilage; these degraded ECM fragments further induce synovial inflammation and inflammatory factor generation, eventually resulting in cartilage damage and OA progression (31).…”

Section: Discussionmentioning

confidence: 99%

“…In the ECM of OA cartilage, MMP-13 is the main degrading enzyme for collagen, and ADAMTS-5 is the major degrading proteinase for aggrecan (32,33). For example, the increased importance of MMP-13 was demonstrated by the observation that MMP-13 overexpression in mouse cartilage resulted in proteoglycans degradation as detected by safranin O staining loss (29). Also, in ADAMTS-5 knock-out mice, a remarkable reduction in articular cartilage destruction in terms of proteoglycan release was found compared to wildtype mice (34).…”

Section: Discussionmentioning

confidence: 99%

Dexamethasone-loaded thermo-sensitive hydrogel attenuates osteoarthritis by protecting cartilage and providing effective pain relief

Wang¹,

Xu²,

Fan³

et al. 2021

Ann Transl Med

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Background: We utilized the destabilization of medial meniscus (DMM)-induced mice to illustrate the osteoarthritis (OA) suppressing and pain-relieving effects of a novel prolonged-release intra-articular (IA)dexamethasone-loaded thermo-sensitive hydrogel (DLTH).Methods: The effects of temperature and pH on DLTH formation and in vitro DLTH release profile were assessed. C57BL/6J mice were randomly divided into three groups: Ctrl group Model group and DLTH group. The DLTH group received joint injections of 10 μL DLTH (1 mg/kg) into the right knee once a week from week 2 to week 11. We performed micro-computed tomography (Micro-CT) and histological analyses of safranin O-fast green, hematoxylin and eosin, and tartrate-resistant acid phosphatase in knee joints. We also carried out immunohistochemical (IHC) staining for matrix metalloproteinase-9 (MMP-9), MMP-13, and a disintegrin and metalloproteinase with thrombospondin motifs-5 in cartilage and Ki-67 in synovia. Pain behavioral testing was carried out in all mice. The serum content of prostaglandin E2 (PGE2) and real-time polymerase chain reaction (PCR) of inflammatory cytokines and pain-related factors in dorsal root ganglia (DRGs) were evaluated. Results: It took 20 minutes to form DLTH at pH 7.0 and 37 ℃. The cumulative release profiles of dexamethasone (Dex) from DLTH at 37 ℃ revealed a rapid release in the first 24 h and a sustained slow release for 7 days. In vivo study illustrated that DLTH attenuated OA bone destruction and ameliorated synovitis and progression of OA in DMM-induced mice. The chondroprotective effects of DLTH were mediated by decreased expressions of MMP-9, MMP-13, and ADAMTS-5. The results showed that IA-DLTH exerted pain-relieving effects in OA mice. Upregulation of nociceptive response time (NRT) and downregulations of serum PGE2, inflammatory factors, and pain-related mediators in DRGs of mice in the DLTH group were recorded. Conclusions: Data presented in this study elucidated that DLTH exhibited a long and lasting Dex release and it is a potential sustainable drug delivery system (DDS) to treat OA locally. IA-DLTH injection exerted chondroprotective and pain-relieving effects in DMM-induced arthritis. The involvement of MMP-9, MMP-13, ADAMTS-5, and inflammatory and pain-related factors, may account for the suppression of OA progression and pain.

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“…Apoptosis, necrosis, chondrocytes aging and loss of proteoglycans were universally acknowledged as the primary features of cartilage injure (17)(18)(19)(20)(21), As direct consequences of these, the density of the living cells in the cartilage decreases. The results of H&E staining veri ed that such a phenomenon really was obvious in the cartilage of OA and KBD.…”

Section: Discussionmentioning

confidence: 99%

ADAMTS4 or ADAMTS5: Which is the Key Enzyme in the Cartilage Degradation of Osteoarthritis and Kashin-Beck Disease?

Meng¹,

Yuan²,

Tan³

et al. 2021

Preprint

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Background: This study aims to investigate the altered expression of a disintegrin and metalloproteinase with thrombospondin motifs 4（ADAMTS4）and a disintegrin and metalloproteinase with thrombospondin motifs 5（ADAMTS5）in the human articular cartilage between osteoarthritis(OA) and Kashin-Beck disease(KBD) and compare their roles in the cartilage injury. Methods: Articular samples were collected from confirmed OA patients and KBD patients then divided into three groups, and the articular cartilages from the normal donors were used as controls. The morphology，location and expression of ADAMTS4 and ADAMTS5 as well as aggrecan were detected by histochemical staining and immunohistochemical staining. Results: Compared to the control, the number of living cells in OA and KBD groups declined at three zones. Meanwhile, the results of toluidine blue staining showed that there was a loss of aggrecan in extracellular matrix of KBD and OA cartilages. The amounts of chondrocytes positively stained for ADAMTS4 were lower in the middle and deep zones of OA and KBD cartilages than those in the control samples. On the contrary, the immunostaining for ADAMTS5 significantly increased in OA and KBD group compared with control group at all three zones. Notably, although there was no statistical significance, the expression of ADAMST5 in KBD was slightly higher than the ones in OA in superficial, middle and deep zones. Conclusions: The role ADAMTS4 acted in aggrecan degradation was seemingly minor. It could be inferred that ADAMTS5 is the key enzyme in the cartilage destruction, particularly in KBD cartilage, which could explain the complex pathogenesis of KBD and provide a potential therapeutic target for KBD patients.

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IL-37 diminishes proteoglycan loss in human OA cartilage: donor-specific link between IL-37 and MMP-3

Cited by 14 publications

References 41 publications

Vitamin D3 protects articular cartilage by inhibiting the Wnt/β‑catenin signaling pathway

Vitamin D3 protects articular cartilage by inhibiting the Wnt/β‑catenin signaling pathway

Dexamethasone-loaded thermo-sensitive hydrogel attenuates osteoarthritis by protecting cartilage and providing effective pain relief

ADAMTS4 or ADAMTS5: Which is the Key Enzyme in the Cartilage Degradation of Osteoarthritis and Kashin-Beck Disease?

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