Intra-articular decorin influences the fibrosis genetic expression profile in a rabbit model of joint contracture

Abdel, Matthew P.; Morrey, Mark E.; Barlow, Jonathan D.; Grill, Diane E.; Kolbert, Christopher P.; An, Kai Nan; Steinmann, Scott P.; Morrey, B.F.; Sanchez-Sotelo, Joaquín

doi:10.1302/2046-3758.33.2000276

Cited by 33 publications

(31 citation statements)

References 34 publications

(46 reference statements)

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“…The clinical relevance of the model we selected is well established and its core design has been adapted by a number of independent research groups. 2,7,[24][25][26][27][28][29][30][31][32] This model was employed as a part of an ongoing study that utilizes subcutaneous pumps to deliver compounds of interest to an injured rabbit. Here, we focused on the fibrotic processes in a group of untreated rabbits in which only phosphate buffered saline (PBS) was applied.…”

Section: Joint Contracture Modelmentioning

confidence: 99%

Auxiliary proteins that facilitate formation of collagen‐rich deposits in the posterior knee capsule in a rabbit‐based joint contracture model

Steplewski

Fertala

Beredjiklian

et al. 2015

Journal Orthopaedic Research

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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 a-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. ß

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Section: Joint Contracture Modelmentioning

confidence: 99%

Auxiliary proteins that facilitate formation of collagen‐rich deposits in the posterior knee capsule in a rabbit‐based joint contracture model

Steplewski

Fertala

Beredjiklian

et al. 2015

Journal Orthopaedic Research

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“…Furthermore, microarray analysis of mRNA has demonstrated that the most notable changes in mRNA expression in capsular tissues occurred within the first 24 to 72 hours after injury. 13,14 Other studies have suggested the possible influence of mast cells on the development of arthrofibrosis in the four weeks after injury. 11 The early onset of changes, both on the cellular and molecular level, seems to indicate the need for early intervention to prevent or abort the development of arthrofibrosis.…”

Section: Introductionmentioning

confidence: 99%

“…15 Decorin, while demonstrating change in the local mRNA expression, did not affect the overall degree of contracture. 13 …”

Section: Introductionmentioning

confidence: 99%

Intra-articular implantation of collagen scaffold carriers is safe in both native and arthrofibrotic rabbit knee joints

Walker

Ewald

Lewallen

et al. 2017

Bone & Joint Research

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ObjectivesSustained intra-articular delivery of pharmacological agents is an attractive modality but requires use of a safe carrier that would not induce cartilage damage or fibrosis. Collagen scaffolds are widely available and could be used intra-articularly, but no investigation has looked at the safety of collagen scaffolds within synovial joints. The aim of this study was to determine the safety of collagen scaffold implantation in a validated in vivo animal model of knee arthrofibrosis.Materials and MethodsA total of 96 rabbits were randomly and equally assigned to four different groups: arthrotomy alone; arthrotomy and collagen scaffold placement; contracture surgery; and contracture surgery and collagen scaffold placement. Animals were killed in equal numbers at 72 hours, two weeks, eight weeks, and 24 weeks. Joint contracture was measured, and cartilage and synovial samples underwent histological analysis.ResultsAnimals that underwent arthrotomy had equivalent joint contractures regardless of scaffold implantation (-13.9° versus -10.9°, equivalence limit 15°). Animals that underwent surgery to induce contracture did not demonstrate equivalent joint contractures with (41.8°) or without (53.9°) collagen scaffold implantation. Chondral damage occurred in similar rates with (11 of 48) and without (nine of 48) scaffold implantation. No significant difference in synovitis was noted between groups. Absorption of the collagen scaffold occurred within eight weeks in all animalsConclusionOur data suggest that intra-articular implantation of a collagen sponge does not induce synovitis or cartilage damage. Implantation in a native joint does not seem to induce contracture. Implantation of the collagen sponge in a rabbit knee model of contracture may decrease the severity of the contracture.Cite this article: J. A. Walker, T. J. Ewald, E. Lewallen, A. Van Wijnen, A. D. Hanssen, B. F. Morrey, M. E. Morrey, M. P. Abdel, J. Sanchez-Sotelo. Intra-articular implantation of collagen scaffold carriers is safe in both native and arthrofibrotic rabbit knee joints. Bone Joint Res 2016;6:162–171. DOI: 10.1302/2046-3758.63.BJR-2016-0193.

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“…The biologic prevention or treatment of arthrofibrosis may provide alternative therapies to improve ROM. Experimental approaches to limit the formation of fibrotic tissue in injured joints have included blocking the profibrotic activity of tissue growth factor β1 (TGF‐β1) with neutralizing antibodies or decorin, inhibiting vascular endothelial growth factor and fibroblast growth factor 2, and applying ketotifen to reduce profibrotic processes in mast cells that invade the injured joint tissues …”

mentioning

confidence: 99%

“…Experimental approaches to limit the formation of fibrotic tissue in injured joints have included blocking the profibrotic activity of tissue growth factor b1 (TGF-b1) with neutralizing antibodies or decorin, inhibiting vascular endothelial growth factor and fibroblast growth factor 2, and applying ketotifen to reduce profibrotic processes in mast cells that invade the injured joint tissues. [4][5][6][7][8][9] In this study, we tested the feasibility of limiting post-traumatic joint contracture by reducing the formation of collagen-rich deposits in the capsules of injured knee joints in rabbits. We aimed to directly interfere with the extracellular process of collagen fibril formation by blocking the critical collagencollagen interaction mediated by the C-terminal telopeptide region of collagen I molecules.…”

mentioning

confidence: 99%

Blocking collagen fibril formation in injured knees reduces flexion contracture in a rabbit model

et al. 2016

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Post-traumatic joint contracture is a frequent orthopaedic complication that limits the movement of injured joints, thereby severely impairing affected patients. Non-surgical and surgical treatments for joint contracture often fail to improve the range of motion. In this study, we tested a hypothesis that limiting the formation of collagen-rich tissue in the capsules of injured joints would reduce the consequences of the fibrotic response and improve joint mobility. We targeted the formation of collagen fibrils, the main component of fibrotic deposits formed within the tissues of injured joints, by employing a relevant rabbit model to test the utility of a custom-engineered antibody. The antibody was delivered directly to the cavities of injured knees in order to block the formation of collagen fibrils produced in response to injury. In comparison to the non-treated control, mechanical tests of the antibody-treated knees demonstrated a significant reduction of flexion contracture. Detailed microscopic and biochemical studies verified that this reduction resulted from the antibody-mediated blocking of the assembly of collagen fibrils. These findings indicate that extracellular processes associated with excessive formation of fibrotic tissue represent a valid target for limiting post-traumatic joint stiffness. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:1038-1046, 2017.

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Intra-articular decorin influences the fibrosis genetic expression profile in a rabbit model of joint contracture

Cited by 33 publications

References 34 publications

Auxiliary proteins that facilitate formation of collagen‐rich deposits in the posterior knee capsule in a rabbit‐based joint contracture model

Auxiliary proteins that facilitate formation of collagen‐rich deposits in the posterior knee capsule in a rabbit‐based joint contracture model

Intra-articular implantation of collagen scaffold carriers is safe in both native and arthrofibrotic rabbit knee joints

Blocking collagen fibril formation in injured knees reduces flexion contracture in a rabbit model

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