OBJECTIVE: The EFEMP1 gene encoding fibulin 3 is specifically expressed in the superficial zone (SZ) of articular cartilage. The aims of this study were to examine the expression patterns of fibulin 3 in the knee joints during aging and during osteoarthritis (OA) and to determine the role of fibulin 3 in the pathogenesis of OA. METHODS: Immunohistochemical analysis was performed on normal and OA knee cartilage samples from humans and mice. Experimental OA was induced in wild-type and fibulin 3-/- mice, and the severity of OA was evaluated by histologic scoring. To examine fibulin 3 function, human chondrocyte monolayer cultures were transfected with small interfering RNA (siRNA), followed by quantitative polymerase chain reaction and Western blot analyses. Human bone marrow-derived mesenchymal stem cells (BM-MSCs) were transduced with an EFEMP1 lentivirus and analyzed for markers of chondrogenesis. RESULTS: Fibulin 3 was specifically expressed in the SZ of normal knee joint cartilage from humans and mice, and the expression levels declined with aging. Both aging-related OA and experimental OA were significantly more severe in fibulin 3-/- mice compared with wild-type mice. Fibulin 3 expression was high in undifferentiated human BM-MSCs and decreased during chondrogenesis. Suppression of fibulin 3 by siRNA significantly increased the expression of SOX9, type II collagen, and aggrecan in human articular chondrocytes, while overexpression of fibulin 3 inhibited chondrogenesis in BM-MSCs. CONCLUSION: Fibulin 3 is specifically expressed in the SZ of articular cartilage and its expression is reduced in aging and OA. Fibulin 3 regulates differentiation of adult progenitor cells, and its aging-related decline is an early event in the pathogenesis of OA. Preventing aging-associated loss of fibulin 3 or restoring it to normal levels in SZ chondrocytes has the potential to delay or prevent the onset of OA.
OBJECTIVE: The EFEMP1 gene encoding fibulin 3 is specifically expressed in the superficial zone (SZ) of articular cartilage. The aims of this study were to examine the expression patterns of fibulin 3 in the knee joints during aging and during osteoarthritis (OA) and to determine the role of fibulin 3 in the pathogenesis of OA. METHODS: Immunohistochemical analysis was performed on normal and OA knee cartilage samples from humans and mice. Experimental OA was induced in wild-type and fibulin 3-/- mice, and the severity of OA was evaluated by histologic scoring. To examine fibulin 3 function, human chondrocyte monolayer cultures were transfected with small interfering RNA (siRNA), followed by quantitative polymerase chain reaction and Western blot analyses. Human bone marrow-derived mesenchymal stem cells (BM-MSCs) were transduced with an EFEMP1 lentivirus and analyzed for markers of chondrogenesis. RESULTS:Fibulin 3 was specifically expressed in the SZ of normal knee joint cartilage from humans and mice, and the expression levels declined with aging. Both aging-related OA and experimental OA were significantly more severe in fibulin 3-/- mice compared with wild-type mice. Fibulin 3 expression was high in undifferentiated human BM-MSCs and decreased during chondrogenesis. Suppression of fibulin 3 by siRNA significantly increased the expression of SOX9, type II collagen, and aggrecan in human articular chondrocytes, while overexpression of fibulin 3 inhibited chondrogenesis in BM-MSCs. CONCLUSION:Fibulin 3 is specifically expressed in the SZ of articular cartilage and its expression is reduced in aging and OA. Fibulin 3 regulates differentiation of adult progenitor cells, and its aging-related decline is an early event in the pathogenesis of OA. Preventing aging-associated loss of fibulin 3 or restoring it to normal levels in SZ chondrocytes has the potential to delay or prevent the onset of OA.
Authors: David D Rahn; Jesús F Acevedo; Shayzreen Roshanravan; Patrick W Keller; Elaine C Davis; Lihua Y Marmorstein; R Ann Word Journal: Am J Pathol Date: 2008-12-18 Impact factor: 4.307
Authors: Noboru Taniguchi; Beatriz Caramés; Lorenza Ronfani; Ulrich Ulmer; Setsuro Komiya; Marco E Bianchi; Martin Lotz Journal: Proc Natl Acad Sci U S A Date: 2009-01-12 Impact factor: 11.205
Authors: Andrea Lolli; Letizia Penolazzi; Roberto Narcisi; Gerjo J V M van Osch; Roberta Piva Journal: Cell Mol Life Sci Date: 2017-04-22 Impact factor: 9.261
Authors: Huub M de Visser; Christelle Sanchez; Simon C Mastbergen; Floris P J G Lafeber; Yves E Henrotin; Harrie Weinans Journal: Cartilage Date: 2018-01-24 Impact factor: 4.634
Authors: Marta Marchini; Mitchell R Ashkin; Melina Bellini; Margaret Man-Ger Sun; Matthew Lloyd Workentine; Hamza Malik Okuyan; Roman Krawetz; Frank Beier; Campbell Rolian Journal: Front Cell Dev Biol Date: 2021-12-14
Authors: Steffi Daniel; Marian Renwick; Viet Q Chau; Shyamtanu Datta; Prabhavathi Maddineni; Gulab Zode; Emma M Wade; Stephen P Robertson; W Matthew Petroll; John D Hulleman Journal: J Mol Med (Berl) Date: 2020-09-22 Impact factor: 4.599
Authors: Kaj E C Blokland; Simon D Pouwels; Michael Schuliga; Darryl A Knight; Janette K Burgess Journal: Clin Sci (Lond) Date: 2020-10-30 Impact factor: 6.124