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 cartilage differentiation and additionally helps to attenuate inflammatory cytokines and further downstream disease-associated pro-inflammatory pathways. Hence, the autologous or allogeneic stem cells and local cartilage tissues may be used for efficient cartilage differentiation and the management of OA.
Highlights
Osteoarthritis (OA) is a common inflammatory and degenerative disease of adult bone joints, and approximately 10–15% of the young and 60% of older people suffer from OA worldwide (Wittenauer et al, 2013)
To understand the possible role of cytokines in OA and its management, we evaluated the secretory factors from an ex vivo osteochondral model, which was used in chondrogenic differentiation of the human bone marrow mesenchymal stem cells (BM-MSCs) for cartilage tissue regeneration
Multiplex Luminex xMAP Assay of Chemokines. Chemokines such as monocyte chemoattractant protein-1 (MCP1), macrophage inhibitory protein-alpha (MIP-α), macrophage inhibitory protein-beta (MIP-β), regulated on activation, normal T cell expressed and secreted (RANTES, C-C chemokines), Eotaxin, and interferon gamma-induced protein 10 (IP10), a C-X-C chemokine, levels were measured in supernatants from control, and experimental groups showed differential secretion pattern upon chondrogenic differentiation (Figures 2A–F)
Summary
Osteoarthritis (OA) is a common inflammatory and degenerative disease of adult bone joints, and approximately 10–15% of the young and 60% of older people suffer from OA worldwide (Wittenauer et al, 2013). Synthetic osteochondral grafts have been used for the treatment of osteochondral lesions (Pearce et al, 2012), and they provide a viable alternative option to both autologous and allogenic grafts but are still under evaluation for their large-scale clinical applications (Jia et al, 2017) Another significantly advanced approach for the healing of damaged articular cartilage is autologous chondrocyte implantation (ACI), which involves arthroscopic removal of a small piece of articular cartilage from the patient’s knee for self-repair. MSCs, along with their differentiation ability, demonstrate immunosuppressive properties mediated via secretion of a variety of soluble factors, including anti-inflammatory cytokines (Zhao et al, 2016) These essential characteristics of MSCs make them highly suitable for allogeneic cell therapy in OA
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