ArticleStem cell research & therapy2020
Inhibition of hypertrophy and improving chondrocyte differentiation by MMP-13 inhibitor small molecule encapsulated in alginate-chondroitin sulfate-platelet lysate hydrogel.
Article in Stem cell research & therapy, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 51 citations in OpenAlex.
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- Coupled Bone-Muscle Degeneration in Chronic Pancreatitis: A Juvenile Porcine Model of Secondary Osteosarcopenia.International journal of molecular sciences · 2025Article
- Promotion of hMDSC differentiation by combined action of scaffold material and TGF-β superfamily growth factors.Regenerative therapy · 2024Article
- Transplantation of Gelatin Microspheres Loaded with Wharton's Jelly Derived Mesenchymal Stem Cells Facilitates Cartilage Repair in Mice.Tissue engineering and regenerative medicine · 2024Article
- Collagen type X expression and chondrocyte hypertrophic differentiation during OA and OS development.American journal of cancer research · 2024Review
- Detrimental alteration of mesenchymal stem cells by an articular inflammatory microenvironment results in deterioration of osteoarthritis.BMC medicine · 2023Article
- Disrupting mechanical homeostasis promotes matrix metalloproteinase-13 mediated processing of neuron glial antigen 2 in mandibular condylar cartilage.European cells & materials · 2023Article
- Chondrocyte Isolation from Loose Bodies-An Option for Reducing Donor Site Morbidity for Autologous Chondrocyte Implantation.International journal of molecular sciences · 2023Article
- New strategy of personalized tissue regeneration: when autologous platelet concentrates encounter biomaterials.Frontiers in bioengineering and biotechnology · 2023Review
- Review
- Engineering hypertrophic cartilage grafts from lipoaspirate for critical-sized calvarial bone defect reconstruction: An adipose tissue-based developmental engineering approach.Bioengineering & translational medicine · 2022Article
- Glutamine exerts a protective effect on osteoarthritis development by inhibiting the Jun N-terminal kinase and nuclear factor kappa-B signaling pathways.Scientific reports · 2022Article
- TRPV4 activation enhances compressive properties and glycosaminoglycan deposition of equine neocartilage sheets.Osteoarthritis and cartilage open · 2022Article
- Functionalized Hydrogels for Cartilage Repair: The Value of Secretome-Instructive Signaling.International journal of molecular sciences · 2022Review
- Advanced 3D-Printing Bioinks for Articular Cartilage Repair.International journal of bioprinting · 2022Review
- Macro, Micro, and Molecular. Changes of the Osteochondral Interface in Osteoarthritis Development.Frontiers in cell and developmental biology · 2021Review
- ADAMTS-12: Functions and Challenges for a Complex Metalloprotease.Frontiers in molecular biosciences · 2021Review
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundMesenchymal stem cells are a promising cell source for chondrogenic differentiation and have been widely used in several preclinical and clinical studies. However, they are prone to an unwanted differentiation process towards hypertrophy that limits their therapeutic efficacy. Matrix metallopeptidase 13 (MMP-13) is a well-known factor regulated during this undesirable event. MMP-13 is a collagen degrading enzyme, which is also highly expressed in the hypertrophic zone of the growth plate and in OA cartilage. Accordingly, we investigated the effect of MMP-13 inhibition on MSC hypertrophy.
methodsIn this study, 5-bromoindole-2-carboxylic acid (BICA) was used as an inhibitory agent for MMP-13 expression. After identifying its optimal concentration, BICA was mixed into a hydrogel and the release rate was studied. To prepare the ideal hydrogel, chondroitin sulfate (CS) and platelet lysate (PL) were mixed with sodium alginate (Alg) at concentrations selected based on synergistic mechanical and rheometric properties. Then, four hydrogels were prepared by combining alginate (1.5%w/v) and/or CS (1%w/v) and/or PL (20%v/v). The chondrogenic potential and progression to hypertrophy of human bone marrow-derived mesenchymal stem cell (hBM-MSC)-loaded hydrogels were investigated under free swelling and mechanical loading conditions, in the presence and absence of BICA.
resultsViability of hBM-MSCs seeded in the four hydrogels was similar. qRT-PCR revealed that BICA could successfully inhibit MMP-13 expression, which led to an inhibition of Coll X and induction of Coll-II, in both free swelling and loading conditions. The GAG deposition was higher in the group combining BICA and mechanical stimulation.
conclusionsIt is concluded that BICA inhibition of MMP-13 reduces MSC hypertrophy during chondrogenesis.
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