title: Fibronectin splice variation in human knee cartilage, meniscus and synovial membrane: observations in osteoarthritic knee.
abstract: Fibronectin (FN) is a widely expressed molecule that can participate in development of osteoarthritis (OA) affecting cartilage, meniscus, and synovial membrane (SM). The alternatively spliced isoforms of FN in joint tissues other than cartilage have not been extensively studied previously. The present study compares FN splice variation in patients with varying degrees of osteoarthritic change. Joint tissues were collected from asymptomatic donors and patients undergoing arthroscopic procedures. Total RNA was amplified by PCR using primers flanking alternatively spliced Extra Domain A (EDA), Extra Domain B (EDB) and Variable (V) regions. EDB(+) , EDB(-) and EDA(-) and V(+) variants were present in all joint tissues, while the EDA(+) variant was rarely detected. Expression levels of EDB(+) and EDV(+) variants were similar in cartilage, synovium, and meniscal tissues. Synovial expression of V(+) FN in arthroscopy patients varied with degree of cartilage degeneration. Two V(-) isoforms, previously identified in cartilage, were also present in SM and meniscus. Fibronectin splicing in meniscus and SM bears striking resemblance to that of cartilage. Expression levels of synovial V(+) FN varied with degree of cartilage degeneration. V(+) FN should be investigated as a potential biomarker of disease stage or progression in larger populations.
authors.affiliation: Division of Rheumatology, Philadelphia Veterans Affairs Medical Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Carla R
authors.initials: CR
authors.lastname: Scanzello
authors.forename: Dessislava Z
authors.initials: DZ
authors.lastname: Markova
authors.forename: Ana
authors.initials: A
authors.lastname: Chee
authors.forename: Yan
authors.initials: Y
authors.lastname: Xiu
authors.forename: Sherrill L
authors.initials: SL
authors.lastname: Adams
authors.forename: Greg
authors.initials: G
authors.lastname: Anderson
authors.forename: Miltiadis
authors.initials: M
authors.lastname: Zgonis
authors.forename: Ling
authors.initials: L
authors.lastname: Qin
authors.forename: Howard S
authors.initials: HS
authors.lastname: An
authors.forename: Yejia
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000328:Adult; D000368:Aged; D017398:Alternative Splicing; D000704:Analysis of Variance; D001706:Biopsy; D002358:Cartilage, Articular / Q000737:chemistry / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005353:Fibronectins / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D008297:Male; D008592:Menisci, Tibial / Q000737:chemistry / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D008875:Middle Aged; D020370:Osteoarthritis, Knee / Q000378:metabolism* / Q000473:pathology; D020033:Protein Isoforms; D012333:RNA, Messenger / Q000302:isolation & purification; D013583:Synovial Membrane / Q000737:chemistry / Q000378:metabolism / Q000473:pathology
chemical_list: D005353:Fibronectins; D020033:Protein Isoforms; D012333:RNA, Messenger
keywords: alternative splicing; cartilage; degeneration; fibronectin; synovium