Age-related nanostructural and nanomechanical changes of individual human cartilage aggrecan monomers and their glycosaminoglycan side chains

被引:42
|
作者
Lee, Hsu-Yi [1 ]
Han, Lin [2 ,3 ]
Roughley, Peter J. [4 ]
Grodzinsky, Alan J. [1 ,5 ,6 ]
Ortiz, Christine [2 ]
机构
[1] MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA
[2] MIT, Dept Mat Sci & Engn, Cambridge, MA 02139 USA
[3] Drexel Univ, Sch Biomed Engn, Philadelphia, PA 19104 USA
[4] McGill Univ, Genet Unit, Shriners Hosp Children, Montreal, PQ H3G 1A6, Canada
[5] MIT, Dept Mech Engn, Cambridge, MA 02139 USA
[6] MIT, Dept Biol Engn, Cambridge, MA 02139 USA
基金
美国国家卫生研究院; 美国国家科学基金会;
关键词
Cartilage; Aggrecan; Glycosaminoglycan; Ultrastructure; Aging; HUMAN ARTICULAR-CARTILAGE; ATOMIC-FORCE MICROSCOPY; CHONDROITIN SULFATE; SUBSTRATE-SPECIFICITY; INTERGLOBULAR DOMAIN; ELECTRON-MICROSCOPY; STRUCTURAL-CHANGES; MOLECULAR-MODEL; CLEAVAGE SITE; IN-VIVO;
D O I
10.1016/j.jsb.2012.12.008
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The nanostructure and nanomechanical properties of aggrecan monomers extracted and purified from human articular cartilage from donors of different ages (newborn, 29 and 38 year old) were directly visualized and quantified via atomic force microscopy (AFM)-based imaging and force spectroscopy. AFM imaging enabled direct comparison of full length monomers at different ages. The higher proportion of aggrecan fragments observed in adult versus newborn populations is consistent with the cumulative proteolysis of aggrecan known to occur in vivo. The decreased dimensions of adult full length aggrecan (including core protein and glycosaminoglycan (GAG) chain trace length, end-to-end distance and extension ratio) reflect altered aggrecan biosynthesis. The demonstrably shorter GAG chains observed in adult full length aggrecan monomers, compared to newborn monomers, also reflects markedly altered biosynthesis with age. Direct visualization of aggrecan subjected to chondroitinase and/or keratanase treatment revealed conformational properties of aggrecan monomers associated with chondroitin sulfate (CS) and keratan sulfate (KS) GAG chains. Furthermore, compressive stiffness of chemically end-attached layers of adult and newborn aggrecan was measured in various ionic strength aqueous solutions. Adult aggrecan was significantly weaker in compression than newborn aggrecan even at the same total GAG density and bath ionic strength, suggesting the importance of both electrostatic and non-electrostatic interactions in nanomechanical stiffness. These results provide molecular-level evidence of the effects of age on the conformational and nanomechanical properties of aggrecan, with direct implications for the effects of aggrecan nanostructure on the age-dependence of cartilage tissue biomechanical and osmotic properties. (c) 2012 Elsevier Inc. All rights reserved.
引用
收藏
页码:264 / 273
页数:10
相关论文
共 50 条
  • [41] Age-related changes in human optokinetic function
    Matheson, AJ
    Darlington, CL
    Smith, PF
    NEUROREPORT, 1998, 9 (10) : 2175 - 2177
  • [42] Age-related changes of elements in human ureter
    Yasuo Takano
    Yoshiyuki Tohno
    Yumi Moriwake
    Setsuko Tohno
    Takeshi Minami
    Masa-oki Yamada
    Kazunari Yuri
    Biological Trace Element Research, 2000, 74 : 117 - 125
  • [43] Age-Related Changes to Human Tear Composition
    Micera, Alessandra
    Di Zazzo, Antonio
    Esposito, Graziana
    Longo, Rosa
    Foulsham, William
    Sacco, Roberto
    Sgrulletta, Roberto
    Bonini, Stefano
    INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, 2018, 59 (05) : 2024 - 2031
  • [44] Age-related changes in angiogenesis in human dermis
    Gunin, Andrei G.
    Petrov, Vadim V.
    Golubtzova, Natalia N.
    Vasilieva, Olga V.
    Kornilova, Natalia K.
    EXPERIMENTAL GERONTOLOGY, 2014, 55 : 143 - 151
  • [45] Age-related changes in the human optic nerve
    Cavallotti, C
    Pacella, E
    Pescolsolido, N
    Tranquilli-Leali, FM
    Feher, J
    CANADIAN JOURNAL OF OPHTHALMOLOGY-JOURNAL CANADIEN D OPHTALMOLOGIE, 2002, 37 (07): : 389 - 394
  • [46] Age-related changes in the human laryngeal glands
    Sato, K
    Hirano, M
    ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY, 1998, 107 (06): : 525 - 529
  • [47] Glycosaminoglycans in the Human Cornea: Age-Related Changes
    Pacella, Elena
    Pacella, Fernanda
    De Paolis, Giulio
    Parisella, Francesca Romana
    Turchetti, Paolo
    Anello, Giulia
    Cavallotti, Carlo
    OPHTHALMOLOGY AND EYE DISEASES, 2015, 7 : 1 - 5
  • [48] Age-related changes of elements in human ureter
    Takano, Y
    Tohno, Y
    Moriwake, Y
    Tohno, S
    Minami, T
    Yamada, MO
    Yuri, K
    BIOLOGICAL TRACE ELEMENT RESEARCH, 2000, 74 (02) : 117 - 125
  • [49] Age-related odontometric changes of human teeth
    Murray, PE
    Stanley, HR
    Matthews, JB
    Sloan, AJ
    Smith, AJ
    ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY ORAL RADIOLOGY AND ENDODONTICS, 2002, 93 (04): : 474 - 482
  • [50] Age-related changes in human meniscal glycosaminoglycans
    Blackburn, G
    Al-Jafary, M
    Huckerby, T
    Lauder, R
    INTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY, 2004, 85 (04) : A57 - A58