title: Auxiliary proteins that facilitate formation of collagen-rich deposits in the posterior knee capsule in a rabbit-based joint contracture model.
abstract: Post-traumatic joint contracture is a debilitating consequence of trauma or surgical procedures. It is associated with fibrosis that develops regardless of the nature of initial trauma and results from complex biological processes associated with inflammation and cell activation. These processes accelerate production of structural elements of the extracellular matrix, particularly collagen fibrils. Although the increased production of collagenous proteins has been demonstrated in tissues of contracted joints, researchers have not yet determined the complex protein machinery needed for the biosynthesis of collagen molecules and for their assembly into fibrils. Consequently, the purpose of our study was to investigate key enzymes and protein chaperones needed to produce collagen-rich deposits. Using a rabbit model of joint contracture, our biochemical and histological assays indicated changes in the expression patterns of heat shock protein 47 and the α-subunit of prolyl 4-hydroxylase, key proteins in processing nascent collagen chains. Moreover, our study shows that the abnormal organization of collagen fibrils in the posterior capsules of injured knees, rather than excessive formation of fibril-stabilizing cross-links, may be a key reason for observed changes in the mechanical characteristics of injured joints. This result sheds new light on pathomechanisms of joint contraction, and identifies potentially attractive anti-fibrotic targets.
authors.affiliation: Department of Orthopaedic Surgery, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania.
authors.forename: Andrzej
authors.initials: A
authors.lastname: Steplewski
authors.affiliation: Department of Orthopaedic Surgery, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania.
authors.forename: Jolanta
authors.initials: J
authors.lastname: Fertala
authors.affiliation: Department of Orthopaedic Surgery, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania.|Rothman Institute of Orthopaedics, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania.
authors.forename: Pedro K
authors.initials: PK
authors.lastname: Beredjiklian
authors.affiliation: Department of Orthopaedic Surgery, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania.|Rothman Institute of Orthopaedics, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania.
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Abboud
authors.affiliation: Department of Orthopaedic Surgery, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania.|Rothman Institute of Orthopaedics, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania.
authors.forename: Mark L Y
authors.initials: ML
authors.lastname: Wang
authors.affiliation: Department of Orthopaedic Surgery, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania.|Rothman Institute of Orthopaedics, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania.
authors.forename: Surena
authors.initials: S
authors.lastname: Namdari
authors.affiliation: Department of Orthopaedic Surgery, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania.|Rothman Institute of Orthopaedics, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Barlow
authors.affiliation: Department of Orthopaedic Surgery, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania.|Rothman Institute of Orthopaedics, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania.
authors.forename: Michael
authors.initials: M
authors.lastname: Rivlin
authors.affiliation: Department of Orthopaedic Surgery, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania.|Rothman Institute of Orthopaedics, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania.
authors.forename: William V
authors.initials: WV
authors.lastname: Arnold
authors.affiliation: Department of Orthopaedic Surgery, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania.
authors.forename: James
authors.initials: J
authors.lastname: Kostas
authors.affiliation: Department of Orthopaedic Surgery, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania.
authors.forename: Cheryl
authors.initials: C
authors.lastname: Hou
authors.affiliation: Department of Orthopaedic Surgery, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania.
authors.forename: Andrzej
authors.initials: A
authors.lastname: Fertala
mesh_terms: D000818:Animals; D003094:Collagen / Q000378:metabolism*; D003286:Contracture / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D005355:Fibrosis; D007718:Knee Injuries / Q000378:metabolism* / Q000473:pathology; D007719:Knee Joint / Q000378:metabolism* / Q000473:pathology; D011506:Proteins / Q000378:metabolism; D011817:Rabbits
chemical_list: D011506:Proteins; D003094:Collagen
keywords: arthrofibrosis; collagen; collagen fibrils; joint contracture; knee; posterior capsule