Intra-articular injection of hyaluronan diminishes loss of chondrocytes in a rat immobilized-knee model.

Joint immobilization is a useful and common treatment modality in orthopedics. However, it also causes unfavorable outcome such as articular cartilage degeneration. Intra-articular injection of hyaluronan has been accepted as a treatment of osteoarthritis, but its effects on immobilized joint remain to be clarified. Hyaluronan is a polysaccharide, distributed ubiquitously in various tissues. In this study, we examined the effect of hyaluronan on the articular cartilage in immobilized joints. The unilateral knee joints of adult male rats were immobilized at 150 degrees in flexion with an internal plate and screws for 1, 2, 4, 6, 8, 12, or 16 weeks (n = 84). Hyaluronan or saline (50 microl/each injection) was administered intra-articularly on the day of surgery and once a week. The articular cartilage from the medial midcondylar region of the knee was obtained, and divided into non-contact, contact and transitional areas (between the non-contact and the contact areas). In each area, a degree of degeneration was evaluated by histomorphometric grading, and measurements of thickness and number of chondrocytes. Histological grading scores in the hyaluronan group were smaller at 12 and 16 weeks compared with those in the saline group. The thickness of the articular cartilage increased in the transitional area in both groups. The number of chondrocytes in the contact and transitional areas gradually decreased, but their number in the hyaluronan group was greater at 12 and 16 weeks compared with that in the saline group. Hyaluronan showed chondroprotective effects on the articular cartilage in a rat immobilized-knee model.

[1]  Yoshifumi Saijo,et al.  Changes of articular cartilage after immobilization in a rat knee contracture model , 2009, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[2]  T. Laurent Hyaluronan Research in Uppsala* , 2007 .

[3]  E. Itoi,et al.  Expression of type I collagen in the capsule of a contracture knee in a rat model , 2007, Upsala journal of medical sciences.

[4]  Y. Saijo,et al.  Increased Elasticity of Capsule After Immobilization in a Rat Knee Experimental Model Assessed by Scanning Acoustic Microscopy , 2006, Upsala journal of medical sciences.

[5]  J. Prieto,et al.  Apoptosis and nitric oxide in an experimental model of osteoarthritis in rabbit after hyaluronic acid treatment , 2005, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[6]  J. Buckwalter,et al.  Hyaluronans in the treatment of osteoarthritis of the knee: evidence for disease-modifying activity. , 2005, Osteoarthritis and cartilage.

[7]  R. Strachan,et al.  Intra-articular hyaluronate in experimental rabbit osteoarthritis can prevent changes in cartilage proteoglycan content. , 2004, Osteoarthritis and cartilage.

[8]  Takashi Nakamura,et al.  Inhibition of interleukin-1β-stimulated production of matrix metalloproteinases by hyaluronan via CD44 in human articular cartilage , 2004 .

[9]  Toshitaka Nakamura,et al.  Apoptosis and p53 expression in chondrocytes relate to degeneration in articular cartilage of immobilized knee joints. , 2003, The Journal of rheumatology.

[10]  E. Stüssi,et al.  The effects of immobilization on the characteristics of articular cartilage: current concepts and future directions. , 2002, Osteoarthritis and cartilage.

[11]  J. Block,et al.  Efficacy and Safety of Intraarticular Sodium Hyaluronate in Knee Osteoarthritis , 2001 .

[12]  Y. Hirasawa,et al.  Effect of hyaluronan on chondrocyte apoptosis and nitric oxide production in experimentally induced osteoarthritis. , 2000, The Journal of rheumatology.

[13]  H. Uhthoff,et al.  Synovial adhesions are more important than pannus proliferation in the pathogenesis of knee joint contracture after immobilization: an experimental investigation in the rat. , 2000, The Journal of rheumatology.

[14]  J. Arokoski,et al.  Remobilization does not fully restore immobilization induced articular cartilage atrophy. , 1999, Clinical orthopaedics and related research.

[15]  Y. Hirasawa,et al.  The effects of hyaluronan on matrix metalloproteinase-3 (MMP-3), interleukin-1beta(IL-1beta), and tissue inhibitor of metalloproteinase-1 (TIMP-1) gene expression during the development of osteoarthritis. , 1999, Osteoarthritis and cartilage.

[16]  R. Moskowitz,et al.  Intraarticular sodium hyaluronate (Hyalgan) in the treatment of patients with osteoarthritis of the knee: a randomized clinical trial. Hyalgan Study Group. , 1998, The Journal of rheumatology.

[17]  R. Coutts,et al.  The effects of hyaluronan during the development of osteoarthritis. , 1997, Osteoarthritis and cartilage.

[18]  K. O'Connor Unweighting Accelerates Tidemark Advancement in Articular Cartilage at the Knee Joint of Rats , 1997, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[19]  L. Ryd,et al.  Intra-articular hyaluronan injections in the treatment of osteoarthritis of the knee: a randomised, double blind, placebo controlled multicentre trial. Hyaluronan Multicentre Trial Group. , 1996, Annals of the rheumatic diseases.

[20]  T. Kikuchi,et al.  Effect of high molecular weight hyaluronan on cartilage degeneration in a rabbit model of osteoarthritis. , 1996, Osteoarthritis and cartilage.

[21]  V. Mow,et al.  Centrifugal and biochemical comparison of proteoglycan aggregates from articular cartilage in experimental joint disuse and joint instability , 1994, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[22]  H. Iwata,et al.  Effect of high-molecular-weight sodium hyaluronate on immobilized rabbit knee. , 1994, Clinical orthopaedics and related research.

[23]  E. Balazs,et al.  Viscosupplementation: a new concept in the treatment of osteoarthritis. , 1993, The Journal of rheumatology. Supplement.

[24]  T. Oegema,et al.  Biochemical changes in articular cartilage after joint immobilization by casting or external fixation , 1989, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[25]  I. Kiviranta,et al.  Softening of canine articular cartilage after immobilization of the knee joint. , 1986, Clinical orthopaedics and related research.

[26]  H. Helminen,et al.  Effects of immobilization on the articular cartilage in young rabbits. A quantitative light microscopic stereological study. , 1986, Clinical orthopaedics and related research.

[27]  A. Engström‐Làurent,et al.  Concentration and molecular weight of sodium hyaluronate in synovial fluid from patients with rheumatoid arthritis and other arthropathies. , 1985, Annals of the rheumatic diseases.

[28]  K. Brandt,et al.  Running inhibits the reversal of atrophic changes in canine knee cartilage after removal of a leg cast. , 1981, Arthritis and rheumatism.

[29]  Sood Sc A study of the effects of experimental immobilisation on rabbit articular cartilage. , 1971 .

[30]  S. Roy Ultrastructure of articular cartilage in experimental immobilization. , 1970, Annals of the rheumatic diseases.

[31]  S. Gault,et al.  Beneficial effect of immobilization of joints in rheumatoid and related arthritides: a splint study using sequential analysis. , 1969, Arthritis and rheumatism.

[32]  E. Balazs,et al.  Hyaluronic acid in synovial fluid. I. Molecular parameters of hyaluronic acid in normal and arthritis human fluids. , 1967, Arthritis and rheumatism.

[33]  W. Akeson,et al.  The connective-tissue response to immobility: a study of the chondroitin-4 and 6-sulfate and dermatan sulfate changes in periarticular connective tissue of control and immobilized knees of dogs. , 1967, Clinical orthopaedics and related research.

[34]  C. Anderson,et al.  DEGENERATION OF IMMOBILIZED KNEE JOINTS IN RATS; HISTOLOGICAL AND AUTORADIOGRAPHIC STUDY. , 1965, The Journal of bone and joint surgery. American volume.

[35]  W. Wettstein,et al.  Ultrastructure of articular cartilage of mice of various ages. , 1961, The American journal of anatomy.

[36]  E. Evans,et al.  Experimental immobilization and remobilization of rat knee joints , 1960 .

[37]  Guy Trudel,et al.  Contrasting alterations of apposed and unapposed articular cartilage during joint contracture formation. , 2005, Archives of physical medicine and rehabilitation.

[38]  P. Ghosh,et al.  The synthesis of hyaluronic acid by human synovial fibroblasts is influenced by the nature of the hyaluronate in the extracellular environment , 2004, Rheumatology International.

[39]  K. M. Chan,et al.  Intra-articular Hyaluronic Acid following Knee Immobilisation for 6 Weeks in Rabbits , 2001, Clinical Rheumatology.

[40]  V. Mow,et al.  Mechanical behavior and biochemical composition of canine knee cartilage following periods of joint disuse and disuse with remobilization. , 1997, Osteoarthritis and cartilage.

[41]  L. Lohmander,et al.  Intra-articular hyaluronan injections inthe treatmentofosteoarthritis oftheknee: a randomised, double blind, placebo controlled multicentre trial , 1996 .

[42]  I. Kiviranta,et al.  WEIGHT-BEARING CONTROLS GLYCOSAMINOGLYCAN CONCENTRATION AND ARTICULAR CARTILAGE THICKNESS IN THE KNEE JOINTS OF YOUNG BEAGLE DOGS , 1988 .

[43]  I. Kiviranta,et al.  Maturation of proteoglycan matrix in articular cartilage under increased and decreased joint loading. A study in young rabbits. , 1987, Connective tissue research.

[44]  S. Woo,et al.  Immobility effects on synovial joints the pathomechanics of joint contracture. , 1980, Biorheology.

[45]  S. Sood A study of the effects of experimental immobilisation on rabbit articular cartilage. , 1971, Journal of anatomy.

[46]  M. C. Hall Cartilage Changes after Experimental Immobilization of the Knee Joint of the Young Rat , 1963 .

[47]  R. Salter,et al.  The Effects of Continuous Compression on Living Articular Cartilage: An Experimental Investigation , 1960 .