title: Mechanical loading of in situ chondrocytes in lapine retropatellar cartilage after anterior cruciate ligament transection.
abstract: The aims of this study were (i) to quantify chondrocyte mechanics in fully intact articular cartilage attached to its native bone and (ii) to compare the chondrocyte mechanics for cells in healthy and early osteoarthritis (OA) tissue. We hypothesized that cells in the healthy tissue would deform less for given articular surface pressures than cells in the early OA tissue because of a loss of matrix integrity in early OA and the associated loss of structural integrity that is thought to protect chondrocytes. Chondrocyte dynamics were quantified by measuring the deformation response of the cells to controlled loading of fully intact cartilage using a custom-designed confocal indentation system. Early OA was achieved nine weeks following transection of the anterior cruciate ligament (ACL) in rabbit knees. Experiments were performed on the retropatellar cartilage of early OA rabbit knees (four joints and 48 cells), the corresponding intact contralateral control knees (four joints and 48 cells) and knees from normal control rabbits (four joints and 48 cells). Nine weeks following ACL transection, articular cartilage of the experimental joints showed substantial increases in thickness, and progression towards OA as assessed using histological grading. Local matrix strains in the superficial zone were greater for the experimental (38 +/- 4%) compared with the contralateral (27 +/- 5%) and normal (28 +/- 4%) joints (p = 0.04). Chondrocyte deformations in the axial and depth directions were similar during indentation loading for all experimental groups. However, cell width increased more for the experimental cartilage chondrocytes (12 +/- 1%) than the contralateral (6 +/- 1%) and normal control chondrocytes (6 +/- 1%; p < 0.001). On average, chondrocyte volume increased with indentation loading in the early OA cartilage (8 +/- 3%, p = 0.001), while it decreased for the two control groups (-8 +/- 2%, p = 0.002 for contralateral and -8 +/- 1%, p = 0.004 for normal controls). We conclude from these results that our hypothesis of cell deformations in the early OA tissue was only partially supported: specifically, changes in chondrocyte mechanics in early OA were direction-specific with the primary axial deformations remaining unaffected despite vastly increased average axial matrix deformations. Surprisingly, chondrocyte deformations increased in early OA in specific transverse directions which have received little attention to date but might be crucial to chondrocyte signalling in early OA.
authors.affiliation: Department of Mechanical and Manufacturing Engineering, Schulich School of Engineering, University of Calgary, Alberta, Canada.
authors.forename: Sang-Kuy
authors.initials: SK
authors.lastname: Han
authors.forename: Ruth
authors.initials: R
authors.lastname: Seerattan
authors.forename: Walter
authors.initials: W
authors.lastname: Herzog
mesh_terms: D000818:Animals; D016118:Anterior Cruciate Ligament / Q000473:pathology*; D001842:Bone and Bones / Q000473:pathology; D002356:Cartilage / Q000473:pathology; D002358:Cartilage, Articular / Q000378:metabolism* / Q000473:pathology*; D019902:Chondrocytes / Q000473:pathology* / Q000502:physiology; D018450:Disease Progression; D005260:Female; D007596:Joints / Q000473:pathology; D010003:Osteoarthritis / Q000150:complications / Q000378:metabolism / Q000473:pathology; D020370:Osteoarthritis, Knee / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D026741:Physical Therapy Modalities / Q000009:adverse effects; D011312:Pressure; D011817:Rabbits