Deciphering the Association of Cytokines, Chemokines, and Growth Factors in Chondrogenic Differentiation of Human Bone Marrow Mesenchymal Stem Cells Using an ex vivo Osteochondral Culture System

Abstract

Osteoarthritis (OA) is a chronic degenerative joint disorder associated with degradation and decreased production of the extracellular matrix, eventually leading to cartilage destruction. Limited chondrocyte turnover, structural damage, and prevailing inflammatory milieu prevent efficient cartilage repair and restoration of joint function. In the present study, we evaluated the role of secreted cytokines, chemokines, and growth factors present in the culture supernatant obtained from an ex vivo osteochondral model of cartilage differentiation using cartilage pellets (CP), bone marrow stem cells (BM-MSCs), and/or BM-MSCs + CP. Multiplex cytokine analysis showed differential secretion of growth factors (G-CSF, GM-CSF, HGF, EGF, VEGF); chemokines (MCP-1, MIP1α, MIP1β, RANTES, Eotaxin, IP-10), pro-inflammatory cytokines (IL-1β, IL-2, IL-5, IL-6, IL-8, TNFα, IL-12, IL-15, IL-17) and anti-inflammatory cytokines (IL-4, IL-10, and IL-13) in the experimental groups compared to the control. In silico analyses of the role of stem cells and CP in relation to the expression of various molecules, canonical pathways and hierarchical cluster patterns were deduced using the Ingenuity Pathway Analysis (IPA) software (Qiagen, United States). The interactions of the cytokines, chemokines, and growth factors that are involved in the cartilage differentiation showed that stem cells, when used together with CP, bring about a favorable cell signaling that supports

Identification of Novel Gene Signatures using Next-Generation Sequencing Data from COVID-19 Infection Models: Focus on Neuro-COVID and Potential Therapeutics

“…Importantly, the cytokine and cytokine receptor interaction and viral protein interaction with the cytokine and cytokine receptors were activated in COVID-infected NHBE cells. Cytokines are important for both innate and adaptive inflammatory host responses, cell differentiation, cell death, growth, repair and development, and cellular homeostasis ( Pushparaj, 2019 ; Bahlas et al, 2020 ; Harakeh et al, 2020 ; Jafri et al, 2020 ; Pushparaj, 2020 ). Studies have shown that several circulating cytokines and chemokines such as TNFα, CXCL-10, IL-6, and IL-8 are differentially expressed during SARS-CoV-2 infection, and this cytokine/chemokine storm likely contributes to the poor prognosis of COVID-19 ( Liu J. et al, 2020 ; Vaninov, 2020 ) .…”

Investigation of anti-osteoporosis mechanisms of Rehmanniae Radix Preparata based on network pharmacology and experimental verification

“…VEGF is an important downstream gene of the HIF-1 signaling pathway, which can promote the formation of osteoclasts and increase the activity of osteoclasts [ 32 , 33 ]. VEGF produced by mature osteoblasts is essential for angiogenesis–osteogenesis coupling [ 34 , 35 ].…”

Unraveling the Catha edulis Extract Effects on the Cellular and Molecular Signaling in SKOV3 Cells

“…Ingenuity Pathway Analysis (IPA) software (Qiagen Inc., MD, United States) has a cutting edge, up to date next generation knowledge base that consists of clarified scientific information from publications, databases, and other relevant resources ( Jafri et al, 2019 ; Bahlas et al, 2020 ). Here, we applied the IPA to functionally annotate the protein clusters and identified biologically significant disease-specific pathways regulated by cathine and cathinone molecular targets.…”