The degradation of cartilage, due to trauma, mechanical load or diseases, results in abundant loss of extracellular matrix (ECM) integrity and development of osteoarthritis (OA). Chondroitin sulfate (CS) is a member of the highly sulfated glycosaminoglycans (GAGs) and a primary component of cartilage tissue ECM. In this study, we aimed to investigate the effect of mechanical load on the chondrogenic differentiation of bone marrow mesenchymal stem cells (BM-MCSs) encapsulated into CS-tyramine-gelatin (CS-Tyr/Gel) hydrogel in order to evaluate the suitability of this composite for OA cartilage regeneration studies in vitro. The CS-Tyr/Gel/BM-MSCs composite showed excellent biointegration on cartilage explants. The applied mild mechanical load stimulated the chondrogenic differentiation of BM-MSCs in CS-Tyr/Gel hydrogel (immunohistochemical collagen II staining). However, the stronger mechanical load had a negative effect on the human OA cartilage explants evaluated by the higher release of ECM components, such as the cartilage oligomeric matrix protein (COMP) and GAGs, compared to the not-compressed explants. Finally, the application of the CS-Tyr/Gel/BM-MSCs composite on the top of the OA cartilage explants decreased the release of COMP and GAGs from the cartilage explants. Data suggest that the CS-Tyr/Gel/BM-MSCs composite can protect the OA cartilage explants from the damaging effects of external mechanical stimuli. Therefore, it can be used for investigation of OA cartilage regenerative potential and mechanisms under the mechanical load in vitro with further perspectives of therapeutic application in vivo.
Articular cartilage is vulnerable to mechanical overload and has limited ability to restore lesions, which leads to the development of chronic diseases such as osteoarthritis (OA). In this study, the chondrogenic responses of human bone marrow mesenchymal stem cells (BMMSCs) and OA cartilage-derived chondrocytes in 3D chondroitin sulfate-tyramine/gelatin (CS-Tyr)/Gel) hydrogels with or without experimental mechanical load have been investigated. Chondrocytes were smaller in size, had slower proliferation rate and higher level of intracellular calcium (iCa2+) compared to BMMSCs. Under 3D chondrogenic conditions in CS-Tyr/Gel with or without TGF-β3, chondrocytes more intensively secreted cartilage oligomeric matrix protein (COMP) and expressed collagen type II (COL2A1) and aggrecan (ACAN) genes but were more susceptible to mechanical load compared to BMMSCs. ICa2+ was more stably controlled in CS-Tyr/Gel/BMMSCs than in CS-Tyr/Gel/chondrocytes ones, through the expression of L-type channel subunit CaV1.2 (CACNA1C) and Serca2 pump (ATP2A2) genes, and their balance was kept more stable. Due to the lower susceptibility to mechanical load, BMMSCs in CS-Tyr/Gel hydrogel may have an advantage over chondrocytes in application for cartilage regeneration purposes. The mechanical overload related cartilage damage in vivo and the vague regenerative processes of OA chondrocytes might be associated to the inefficient control of iCa2+ regulating channels.
The present study aims to explore the stressed state of cartilage using various meniscal tear models. To perform this research, the anatomical model of the knee joint was developed and the nonlinear mechanical properties of the cartilage and meniscus were verified. The stress–strain curve of the meniscus was obtained by testing fresh tissue specimens of the human meniscus using a compression machine. The results showed that the more deteriorated meniscus had greater stiffness, but its integrity had the greatest impact on the growth of cartilage stresses. To confirm this, cases of radial, longitudinal, and complex tears were examined. The methodology and results of the study can assist in medical diagnostics for meniscus treatment and replacement.
Background Articular cartilage is an avascular tissue with limited capacity to self-regeneration, which leads to challenges treating injuries or diseases such as osteoarthritis (OA). Mesenchymal stem cells (MSCs) are a promising tool for cartilage tissue engineering, as they are capable to differentiate into chondrogenic lineage cells and secrete a number of active molecules important for stimulating chondrocyte anabolic pathways and modulate the metabolism of cartilage extracellular matrix (ECM). Bone marrow-derived MSCs (BMMSCs) are the most widely used for development of cartilage tissue regeneration technologies, however, other sources of stem cells, like menstrual blood, may have advantages due to the ease of access. The aim of this study was to evaluate the potential of menstrual blood-derived MSC (MenSC) paracrine factors in stimulating BMMSCs chondrogenic differentiation and to investigate their role in protecting cartilage from degradation under inflammatory conditions in vitro.Methods In this study, we induced MenSCs and BMMSCs chondrogenic differentiation, using four different growth factors, important for stimulation of chondrogenesis in MSCs – transforming growth factor β-3 (TGF-β3), activin A, bone morphogenetic protein 2 (BMP-2) and insulin growth factor 1 (IGF-1). We stimulated chondrogenic differentiation in BMMSCs co-cultured with MenSCs or cartilage explants co-cultured with MenSCs for 21 days under inflammatory conditions. After, we evaluated chondrogenic capacity of BMMSCs in co-cultures by immunohistochemical staining, secretion of four growth factors and cartilage oligomeric matrix protein, as well as measured release and synthesis of cartilage extracellular matrix proteins and gene expression in cartilage explants after co-culturing them with MenSCs.Results Our results suggest that MenSCs stimulate chondrogenic response in BMMSCs by secreting activin A and TGF-β3, and may have protective effects on cartilage tissue ECM by decreasing release of GAGs into medium, most likely through modulation of activin A related molecular pathway.Conclusion In conclusion, paracrine factors secreted by MenSCs may turn out to be a promising therapeutical approach for cartilage tissue protection and repair.
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