Depletion of chondrocyte primary cilia reduces the compressive modulus of articular cartilage

被引:36
作者
Irianto, Jerome [1 ,2 ]
Ramaswamy, Girish [4 ]
Serra, Rosa [3 ]
Knight, Martin M. [1 ,2 ]
机构
[1] Queen Mary Univ London, Inst Bioengn, London E1 4NS, England
[2] Queen Mary Univ London, Sch Engn & Mat Sci, London E1 4NS, England
[3] UAB, Sch Med & Dent, Arthritis & Musculoskeletal Dis Ctr, Birmingham, AL USA
[4] Univ Penn, Perelman Sch Med, Dept Orthoped Surg, Philadelphia, PA 19104 USA
基金
英国惠康基金;
关键词
Primary cilia; Chondrocyte; Cartilage; Biomechanics; UNCONFINED COMPRESSION; CONFINED COMPRESSION; INDENTATION TESTS; GROWTH-PLATE; OSTEOARTHRITIS; RATIO;
D O I
10.1016/j.jbiomech.2013.11.040
中图分类号
Q6 [生物物理学];
学科分类号
071011 ;
摘要
Primary cilia are slender, microtubule based structures found in the majority of cell types with one cilium per cell. In articular cartilage, primary cilia are required for chondrocyte mechanotransduction and the development of healthy tissue. Loss of primary cilia in Col2aCre;ift88(fi/fi) transgenic mice results in upregulation of osteoarthritic (OA) markers and development of OA like cartilage with greater thickness and reduced mechanical stiffness. However no previous studies have examined whether loss of primary cilia influences the intrinsic mechanical properties of articular cartilage matrix in the form of the modulus or just the structural properties of the tissue. The present study describes a modified analytical model to derive the viscoelastic moduli based on previous experimental indentation data. Results show that the increased thickness of the articular cartilage in the Col2aCre;ift88(fi/fi) transgenic mice is associated with a reduction in both the instantaneous and equilibrium moduli at indentation strains of greater than 20%. This reveals that the loss of primary cilia causes a significant reduction in the mechanical properties of cartilage particularly in the deeper zones and possibly the underlying bone. This is consistent with histological analysis and confirms the importance of primary cilia in the development of a mechanically functional articular cartilage. (C) 2013 The Authors. Published by Elsevier Ltd. All rights reserved.
引用
收藏
页码:579 / 582
页数:4
相关论文
共 24 条
[1]   The Primary Cilium as a Complex Signaling Center [J].
Berbari, Nicolas F. ;
O'Connor, Amber K. ;
Haycraft, Courtney J. ;
Yoder, Bradley K. .
CURRENT BIOLOGY, 2009, 19 (13) :R526-R535
[2]   Compressive properties of mouse articular cartilage determined in a novel micro-indentation test method and biphasic finite element model [J].
Cao, Li ;
Youn, Inchan ;
Guilak, Farshid ;
Setton, Lori A. .
JOURNAL OF BIOMECHANICAL ENGINEERING-TRANSACTIONS OF THE ASME, 2006, 128 (05) :766-771
[3]   Depletion of primary cilia in articular chondrocytes results in reduced Gli3 repressor to activator ratio, increased Hedgehog signaling, and symptoms of early osteoarthritis [J].
Chang, C. -F ;
Ramaswamy, G. ;
Serra, R. .
OSTEOARTHRITIS AND CARTILAGE, 2012, 20 (02) :152-161
[4]   Ift88 regulates Hedgehog signaling, Sfrp5 expression, and β-catenin activity in post-natal growth plate [J].
Chang, Ching-Fang ;
Serra, Rosa .
JOURNAL OF ORTHOPAEDIC RESEARCH, 2013, 31 (03) :350-356
[5]   Altered Trabecular Bone Structure and Delayed Cartilage Degeneration in the Knees of Collagen VI Null Mice [J].
Christensen, Susan E. ;
Coles, Jeffrey M. ;
Zelenski, Nicole A. ;
Furman, Bridgette D. ;
Leddy, Holly A. ;
Zauscher, Stefan ;
Bonaldo, Paolo ;
Guilak, Farshid .
PLOS ONE, 2012, 7 (03)
[6]   Orientation of Primary Cilia of Articular Chondrocytes in Three-Dimensional Space [J].
Farnum, Cornelia E. ;
Wilsman, Norman J. .
ANATOMICAL RECORD-ADVANCES IN INTEGRATIVE ANATOMY AND EVOLUTIONARY BIOLOGY, 2011, 294 (03) :533-549
[7]   MATHEMATICAL-ANALYSIS FOR INDENTATION TESTS OF ARTICULAR-CARTILAGE [J].
HAYES, WC ;
HERRMANN, G ;
MOCKROS, LF ;
KEER, LM .
JOURNAL OF BIOMECHANICS, 1972, 5 (05) :541-&
[8]   Ultrastructural, tomographic and confocal imaging of the chondrocyte primary cilium in situ [J].
Jensen, CG ;
Poole, CA ;
McGlashan, SR ;
Marko, M ;
Issa, ZI ;
Vujcich, KV ;
Bowser, SS .
CELL BIOLOGY INTERNATIONAL, 2004, 28 (02) :101-110
[9]   Biomechanical, biochemical and structural correlations in immature and mature rabbit articular cartilage [J].
Julkunen, P. ;
Harjula, T. ;
Iivarinen, J. ;
Marjanen, J. ;
Seppanen, K. ;
Narhi, T. ;
Arokoski, J. ;
Lammi, M. J. ;
Brama, P. A. ;
Jurvelin, J. S. ;
Helminen, H. J. .
OSTEOARTHRITIS AND CARTILAGE, 2009, 17 (12) :1628-1638
[10]   Optical and mechanical determination of Poisson's ratio of adult bovine humeral articular cartilage [J].
Jurvelin, JS ;
Buschmann, MD ;
Hunziker, EB .
JOURNAL OF BIOMECHANICS, 1997, 30 (03) :235-241