Matrix Metalloproteinase 3: A Promoting and Destabilizing Factor in the Pathogenesis of Disease and Cell Differentiation

Wan, Jiangtao; Zhang, Guowei; Li, Xin; Qiu, Xianshuai; Ouyang, Jun; Dai, Jingxing; Min, Shaoxiong

doi:10.3389/fphys.2021.663978

Cited by 72 publications

(54 citation statements)

References 82 publications

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“…Among them, matrix metalloproteinases MMP-3 and MMP-13 can further promote cartilage inflammation, chondrocyte apoptosis, and ROS production, via a positive feedback loop [ 71 , 72 ]. Emerging evidence has shown that MMP13 is considered a significant biomarker to assess OA therapeutic effects and OA progression [ 73 , 74 ]. In this context, bioactive molecules able to suppress these inflammatory mediators or block the involved signaling pathway may help to reduce the OA pathological process [ 75 ].…”

Section: Resultsmentioning

confidence: 99%

Thermo-Responsive Gel Containing Hydroxytyrosol-Chitosan Nanoparticles (Hyt@tgel) Counteracts the Increase of Osteoarthritis Biomarkers in Human Chondrocytes

Valentino¹,

Conte²,

Luca³

et al. 2022

Antioxidants

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Although osteoarthritis (OA) is a chronic inflammatory degenerative disease affecting millions of people worldwide, the current therapies are limited to palliative care and do not eliminate the necessity of surgical intervention in the most severe cases. Several dietary and nutraceutical factors, such as hydroxytyrosol (Hyt), have demonstrated beneficial effects in the prevention or treatment of OA both in vitro and in animal models. However, the therapeutic application of Hyt is limited due to its poor bioavailability following oral administration. In the present study, a localized drug delivery platform containing a combination of Hyt-loading chitosan nanoparticles (Hyt-NPs) and in situ forming hydrogel have been developed to obtain the benefits of both hydrogels and nanoparticles. This thermosensitive formulation, based on Pluronic F-127 (F-127), hyaluronic acid (HA) and Hyt-NPs (called Hyt@tgel) presents the unique ability to be injected in a minimally invasive way into a target region as a freely flowing solution at room temperature forming a gel at body temperature. The Hyt@tgel system showed reduced oxidative and inflammatory effects in the chondrocyte cellular model as well as a reduction in senescent cells after induction with H2O2. In addition, Hyt@tgel influenced chondrocytes gene expression under pathological state maintaining their metabolic activity and limiting the expression of critical OA-related genes in human chondrocytes treated with stressors promoting OA-like features. Hence, it can be concluded that the formulated hydrogel injection could be proposed for the efficient and sustained Hyt delivery for OA treatment. The next step would be the extraction of “added-value” bioactive polyphenols from by-products of the olive industry, in order to develop a green delivery system able not only to enhance the human wellbeing but also to promote a sustainable environment.

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Section: Resultsmentioning

confidence: 99%

Thermo-Responsive Gel Containing Hydroxytyrosol-Chitosan Nanoparticles (Hyt@tgel) Counteracts the Increase of Osteoarthritis Biomarkers in Human Chondrocytes

Valentino¹,

Conte²,

Luca³

et al. 2022

Antioxidants

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“…However, in the same condition the concentrations of other important factors for vascularization angiopoietin-1 and 2 tended to be relatively low. MMP-3, which is involved in the degradation of cartilage [42], and MMP-9, the in bone most abundant MMP also involved in endochondral ossification [43,44], tended to be relatively high in scaffolds of which defects were implanted with cartilage spheres. However, none of these concentrations differed significantly from the concentrations measured in the other conditions.…”

Section: Resultsmentioning

confidence: 99%

Evaluating material-driven regeneration in a tissue engineered humanin vitrobone defect model

Wildt

Cramer

Silva

et al. 2022

Preprint

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Advanced in vitro human bone defect models can contribute to the evaluation of materials for in situ bone regeneration, addressing both translational and ethical concerns regarding animal models. In this study, we attempted to develop such a model to study material-driven regeneration, using a tissue engineering approach. By co-culturing human umbilical vein endothelial cells (HUVECs) with human bone marrow-derived mesenchymal stromal cells (hBMSCs) on silk fibroin scaffolds with in vitro critically sized defects, the growth of vascular-like networks and three-dimensional bone-like tissue was facilitated. After a model build-up phase of 28 days, materials were artificially implanted and HUVEC and hBMSC migration, cell-material interactions, and osteoinduction were evaluated 14 days after implantation. The materials physiologically relevant for bone regeneration included a platelet gel as blood clot mimic, cartilage spheres as soft callus mimics, and a fibrin gel as control. Although the in vitro model was limited in the evaluation of immune responses, hallmarks of physiological bone regeneration were observed in vitro. These included the endothelial cell chemotaxis induced by the blood clot mimic and the mineralization of the soft callus mimic. Therefore, the present in vitro model could contribute to an improved pre-clinical evaluation of biomaterials while reducing the need for animal experiments.

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“…On the other hand, TIMP-1 has an antagonistic function against MMP-3. Under the physiological condition, there is a balance between MMPs and TIMP-1, and any increase in TIMP-1 with or without a decrease in MMP can lead to an increase in ECM [ 68 ]. Following the P. gingivalis treatment in our study, neither MMP-3 nor TIMP-1 expression in H-GMSCs was modified, whereas MMP-3 and MMP-3/TIMP-1 ratio was significantly increased in most P-GMSC lines, all of which suggests that pathological degradation of ECM within periodontal tissues is more pronounced in the advanced stage of periodontitis.…”

Section: Discussionmentioning

confidence: 99%

Mesenchymal Stromal Cells from Healthy and Inflamed Human Gingiva Respond Differently to Porphyromonas gingivalis

Bekić

Radanović

Đokić

et al. 2022

IJMS

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Gingiva-Derived Mesenchymal Stromal Cells (GMSCs) have been shown to play an important role in periodontitis. However, how P. gingivalis, one of the key etiological agents of the disease, affects healthy (H)- and periodontitis (P)-GMSCs is unknown. To address this problem, we established 10 H-GMSC and 12 P-GMSC lines. No significant differences in morphology, differentiation into chondroblasts and adipocytes, expression of characteristic MSCS markers, including pericyte antigens NG2 and PDGFR, were observed between H- and P-GMSC lines. However, proliferation, cell size and osteogenic potential were higher in P-GMSCs, in contrast to their lower ability to suppress mononuclear cell proliferation. P. gingivalis up-regulated the mRNA expression of IL-6, IL-8, MCP-1, GRO-α, RANTES, TLR-2, HIF-1α, OPG, MMP-3, SDF-1, HGF and IP-10 in P-GMSCs, whereas only IL-6, MCP-1 and GRO-α were up-regulated in H-GMSCs. The expression of MCP-1, RANTES, IP-10 and HGF was significantly higher in P-GMSCs compared to H-GMSCs, but IDO1 was lower. No significant changes in the expression of TLR-3, TLR-4, TGF-β, LAP, IGFBP4 and TIMP-1 were observed in both types of GMSCs. In conclusion, our results suggest that P-GMSCs retain their pro-inflammatory properties in culture, exhibit lower immunosuppressive potential than their healthy counterparts, and impaired regeneration-associated gene induction in culture. All these functions are potentiated significantly by P. gingivalis treatment.

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Matrix Metalloproteinase 3: A Promoting and Destabilizing Factor in the Pathogenesis of Disease and Cell Differentiation

Cited by 72 publications

References 82 publications

Thermo-Responsive Gel Containing Hydroxytyrosol-Chitosan Nanoparticles (Hyt@tgel) Counteracts the Increase of Osteoarthritis Biomarkers in Human Chondrocytes

Thermo-Responsive Gel Containing Hydroxytyrosol-Chitosan Nanoparticles (Hyt@tgel) Counteracts the Increase of Osteoarthritis Biomarkers in Human Chondrocytes

Evaluating material-driven regeneration in a tissue engineered humanin vitrobone defect model

Mesenchymal Stromal Cells from Healthy and Inflamed Human Gingiva Respond Differently to Porphyromonas gingivalis

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