TSG-6- a double-edged sword for osteoarthritis

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TSG-6- a double-edged sword for osteoarthritis C.-H. Chou, D.E. Attarian, H.-G. Wisniewski, P. Band, V.B. Kraus Osteoarthritis and Cartilage Volume 25, (April 2017) DOI: 10.1016/j.joca.2017.02.087 Copyright © 2017 Terms and Conditions

Fig. 1 TSG-6 transfer activity in synovial fluid of OA knees. Synovial fluids (pooled from n = 20 from TKA cohort) from OA joints contain HA-HC, lαl, and TSG-6. (A) The top and bottom panels represent the sample constituents prior to exposure to immobilized HA; the middle panel represents HC1 transferred to HA by endogenous TSG-6 from lαl upon exposure to immobilized HA. (B) The amount of HC1 transferred did not change when samples were pre-treated with hyaluronidase suggesting endogenous HA-HC is unlikely to contribute to the HC transferred to immobilized HA. (C) TSG-6 activity in OA SFs was significantly correlated with the concentration of TSG-6 protein as measured by ELISA. Therefore, the amount of endogenous TSG-6 in SF refects the level of HC transfer to immobilized HA. Osteoarthritis and Cartilage 2017 25, DOI: (10.1016/j.joca.2017.02.087) Copyright © 2017 Terms and Conditions

Fig. 2 Immunolocalization of HC1 and TSG-6 in HA-rich matrices of lesioned and non-lesioned regions of OA cartilages including tibial plateau and meniscus. Antibodies against HC1 and TSG-6 were used to detect their protein expression (dark brown staining) by immunohistochemistry in the HA-rich matrices of cartilage from (A) tibial plateau and (B) meniscus. High expression levels of HC1 (yellow triangles) and TGS-6 (red arrows) were mainly detected and co-localized on the surface of damaged cartilage, with none or much less detected in intact cartilage. Non-immune IgGs were used as negative controls. All sections were counterstained light blue with hematoxylin. The scale bars are 0.3 mm. Osteoarthritis and Cartilage 2017 25, DOI: (10.1016/j.joca.2017.02.087) Copyright © 2017 Terms and Conditions

Fig. 3 Expression of TSG-6 and lαl complex related genes in OA cartilage from joint replacement. TSG-6 was highly and significantly differentially expressed in chondrocytes from damaged cartilage (red) compared to intact cartilage (blue) in (A) tibial plateau and (B) meniscus. ITIH1, ITIH2, ITIH3, and AMBP (bikunin) were either not expressed or expressed at a low level in cartilage. NC represents the level of expression of a negative control with water in lieu of primers. Cts were defined as 40. FC = fold-change. P values were determined by two-tailed paired Student t-tests. N = 20 knee articular cartilages (AC); N = 12 in menisci. Osteoarthritis and Cartilage 2017 25, DOI: (10.1016/j.joca.2017.02.087) Copyright © 2017 Terms and Conditions

Fig. 4 Pre-incubation of HA with TSG-6 reduces binding of HABP to HA, but HA-HC formation reduced this negative effect. Osteoarthritis and Cartilage 2017 25, DOI: (10.1016/j.joca.2017.02.087) Copyright © 2017 Terms and Conditions