Effect of GDF-5 on ligament healing.
The effects of growth and differentiation factor-5 (GDF-5) on ligament healing were studied using a gap injury model of the medial collateral ligament in rat knee joints. The administration of GDF-5 once at the time of surgery significantly improved the mechanical properties of the femur-ligament-tibia complex. At 3 weeks after surgery, 30 microg of GDF-5 improved the ultimate tensile strength of the complex by 41%, and the stiffness by 60%, compared with the vehicle control (p < 0.05 for both; Fisher's PLSD test). The observation with a transmission electron microscopy revealed that GDF-5 increased the diameter of collagen fibrils in the repair tissue, which was considered to be a possible mechanism for the positive result in the biomechanical testing. Quantitative PCR and in situ hybridization revealed enhanced type I procollagen expression by GDF-5, and the PCR analysis also revealed that the GDF-5 treatment reduced the expression of type III procollagen relative to type I procollagen. The PCR analysis further showed that the expression of decorin and fibromodulin was relatively reduced against type I procollagen by the growth factor, which was considered to be responsible for the increase of collagen fibril diameter in the repair tissue. No adverse effects were observed, and the use of GDF-5 was considered a promising approach to facilitate ligament healing.
Tashiro
Toshiyuki
T
Department of Orthopaedic Surgery, JR Tokyo General Hospital, Yoyogi 2-1-3, Shibuya-ku, Tokyo 150-0053, Japan.
Hiraoka
Hisatada
H
Ikeda
Yasuko
Y
Ohnuki
Toshiyuki
T
Suzuki
Ryuji
R
Ochi
Takahiro
T
Nakamura
Kozo
K
Fukui
Naoshi
N
D000818:Animals; D001696:Biomechanical Phenomena; D019485:Bone Morphogenetic Proteins / Q000494:pharmacology*; D011508:Chondroitin Sulfate Proteoglycans / Q000096:biosynthesis; D058575:Decorin; D016326:Extracellular Matrix Proteins / Q000096:biosynthesis; D000071235:Fibromodulin; D055428:Growth Differentiation Factor 5; D017403:In Situ Hybridization; D007632:Keratan Sulfate / Q000096:biosynthesis; D008023:Ligaments, Articular / Q000187:drug effects / Q000293:injuries* / Q000648:ultrastructure; D000071234:Lumican; D008297:Male; D011347:Procollagen / Q000032:analysis; D011509:Proteoglycans / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014945:Wound Healing / Q000187:drug effects*
D019485:Bone Morphogenetic Proteins; D011508:Chondroitin Sulfate Proteoglycans; C546880:Dcn protein, rat; D058575:Decorin; D016326:Extracellular Matrix Proteins; C000604334:Fmod protein, rat; D055428:Growth Differentiation Factor 5; C000604308:Lum protein, rat; D000071234:Lumican; D011347:Procollagen; D011509:Proteoglycans; D000071235:Fibromodulin; D007632:Keratan Sulfate