Abstract
Osteoarthritis (OA) is a degenerative and inflammatory joint disorder with cartilage loss. Dental pulp stem cells (DPSCs) can undergo chondrogenic differentiation and secrete growth factors associated with tissue repair and immunomodulation. Leukocyte- and platelet-rich fibrin (L-PRF) emerges in regenerative medicine because of its growth factor content and fibrin matrix. This study evaluates the therapeutic application of DPSCs and L-PRF in OA via immunomodulation and cartilage regeneration. Chondrogenic differentiation of DPSCs, with or without L-PRF exudate (ex) and conditioned medium (CM), and of bone marrow-mesenchymal stem cells was compared. These cells showed differential chondrogenesis. L-PRF was unable to increase cartilage-associated components. Immature murine articular chondrocytes (iMACs) were cultured with L-PRF ex, L-PRF CM, or DPSC CM. L-PRF CM had pro-survival and proliferative effects on unstimulated and cytokine-stimulated iMACs. L-PRF CM stimulated the release of IL-6 and PGE2, and increased MMP-13, TIMP-1 and IL-6 mRNA levels in cytokine-stimulated iMACs. DPSC CM increased the survival and proliferation of unstimulated iMACs. In cytokine-stimulated iMACs, DPSC CM increased TIMP-1 gene expression, whereas it inhibited nitrite release in 3D culture. We showed promising effects of DPSCs in an in vitro OA model, as they undergo chondrogenesis in vitro, stimulate the survival of chondrocytes and have immunomodulatory effects.
Highlights
Articular cartilage (AC) plays key roles in the function of diarthrodial joints [1,2].Cartilage injuries are very common, predominantly in young and active athletes, and in the knee joint [3,4,5]
In order to compare the chondrogenic differentiation potential between human Dental pulp stem cells (DPSCs) and BM-mesenchymal stem cells (MSCs), cells were subjected to a 3D chondrogenic differentiation system over 21 days
The present study aimed to investigate the chondrogenic potential of both Leukocyte- and platelet-rich fibrin (L-PRF) and DPSCs in vitro in terms of being able to replace lost cartilage tissue, while having chondroprotective and immunomodulatory influences in OA chondrocytes
Summary
Cartilage injuries are very common, predominantly in young and active athletes, and in the knee joint [3,4,5]. They are often considered as risk factors for the development of osteoarthritis (OA) in later life, a degenerative and inflammatory condition of the synovial joint with irreversible cartilage loss [2]. In people over 60 years of age, it is estimated that 9.6% of men and 18% of women have symptomatic OA [8]. Long-lasting regeneration of damaged AC remains an unmet clinical need. With the aim to restore the damaged cartilage tissue, matrix-induced autologous chondrocyte implantation (MACI), a Food and
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