Progranulin plays a chondroprotective role in a surgically-induced osteoarthritis in mice through TNFR2 pathway J. Wei, Y. Zhao, C. Liu Osteoarthritis.

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Progranulin plays a chondroprotective role in a surgically-induced osteoarthritis in mice through TNFR2 pathway J. Wei, Y. Zhao, C. Liu Osteoarthritis and Cartilage Volume 23, Pages A43-A44 (April 2015) DOI: 10.1016/j.joca.2015.02.097 Copyright © 2015 Terms and Conditions

Fig. 1. Deficiency of progranulin (PGRN) led to exaggerated osteoarthritis (OA) progression in a surgically induced model. (A) PGRN-deficient mice exhibited accelerated degeneration of articular cartilage compared with wild type (WT) littermates, assayed by Safranin O staining. Red arrows indicated cartilage destruction. Scale bar=100μm. (B) PGRN deficient mice dispayed a significantly higher score of OA after destabilisation of medial meniscus (DMM) operation on the basis of Safranin O staining. (C) PGRN-deficient mice presented a significantly higher level of cartilage oligomeric matrix protein (COMP) fragment in serum after induction of DMM model, assayed by ELISA. (D) phenotypes of synovium and osteophyte in DMM models established in WT and PGRN-deficient mice at 4 weeks. (a,b) HE staining of knee joints samples from DMM models established in WT and PGRN-/- mice. Black arrows indicate osteophyte formation. (c, d) Magnified field of osteophyte and synovium in WT and PGRN-deficient groups. Black arrows indicate osteophyte formation, and blue arrows indicater synovium, Scale bar=100μm. (E) immunohistochemistry staining also showed stronger positive signals for col X, matrix metalloproteinase (MMP)13 and COMP fragments in PGRN-deficient group than WT group 8 weeks after DMM operation. Scale bar=50μm. Osteoarthritis and Cartilage 2015 23, A43-A44DOI: (10.1016/j.joca.2015.02.097) Copyright © 2015 Terms and Conditions

Fig. 2. Recombinant progranulin (PGRN) attenuated osteoarthritis (OA) development through the TNFR2 pathway in vivo. (A) Intra-articular Injection of PGRN dramatically protected cartilage from degeneration following surgically induced OA model, assayed by Safranin O staining. Scale bar, 100 μm. (B) Phenotypes of synovium and osteophyte in ACLT models at 4 weeks treated with PBS and recombinant PGRN protien (a, c) HE staining of knee Joints samples from ACLT models treated with PBS and recombinant PGRN protein. Black arrows indicate synovium, and blue arrow indicates osteophyte formation in PBS treated ACLT model. (b, d) Magnified field of synovium in PBS and PGRN treated groups. Scale bar, 100 μm, (C) Osteoarthritis Research Society International (OARSI) score of OA, (D) The loss of Aggrecan based on the result of Safranin O staining. (E) Treatment of PGRN reduced serum level of cartilage oligomeric matrix protein (COMP) fragments in ACLT model, assayed by ELISA. Osteoarthritis and Cartilage 2015 23, A43-A44DOI: (10.1016/j.joca.2015.02.097) Copyright © 2015 Terms and Conditions