Conditioned medium from stem cells of human exfoliated deciduous teeth partially alters the expression of inflammation-associated molecules of mouse condylar chondrocytes via secreted frizzled-related protein 1

Intravenous administration of conditioned medium from stem cells of human exfoliated deciduous teeth (SHED-CM) effectively restores mechanically injured osteochondral tissues in mouse temporomandibular joint osteoarthritis. However, the underlying therapeutic mechanisms remain elusive. Here, we investigated the direct therapeutic effects of SHED-CM on inflamed primary condylar chondrocytes in vitro. Immunofluorescence staining revealed that interleukin-1β-stimulated chondrocytes showed increased expression of the catabolic marker inducible nitric oxide synthase (iNOS) and reduced expression of the anabolic marker aggrecan (ACAN). We found that SHED-CM treatment, but not conditioned medium from bone marrow mesenchymal stem cells (BMSC-CM), effectively suppressed iNOS expression and elevated ACAN levels, indicating that SHED-CM converted the catabolic phenotype of inflamed chondrocytes to an anabolic phenotype. Liquid chromatography with tandem mass spectrometry analysis of SHED-CM and BMSC-CM identified eight proteins enriched in SHED-CM that are related to anti-inflammatory and/or chondrogenic processes. Of these proteins, the Wnt signal inhibitor secreted frizzled-related protein 1 (SFRP1) was the most abundantly enriched in SHED-CM. We found that treatment with the selective SFRP1 inhibitor WAY-316606 abolished the anti-catabolic and pro-anabolic effects of SHED-CM. Collectively, our study suggests that SHED-CM directly suppresses catabolism and promotes anabolic responses of inflamed primary condylar chondrocytes, which partially rely on SFRP1 function in SHED-CM. The direct action of SHED-CM may be useful to treat inflammatory cartilage diseases.

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本論文は，著者Linze Xiaの学位論文として提出され，学位審査・授与の対象となっている。