title: Effects of releasing recombinant human growth and differentiation factor-5 from poly(lactic-co-glycolic acid) microspheres for repair of the rat degenerated intervertebral disc.
abstract: The objective of this study was to investigate the therapeutic potential of poly(lactic-co-glycolic acid) (PLGA) microspheres loaded with recombinant human growth and differentiation factor-5 (rhGDF-5) on the disc degeneration induced by needle puncture in a rat caudal disc model.
  
  
  
  The rhGDF-5-loaded PLGA microspheres were prepared by the water-oil-water double-emulsion solvent evaporation method, and release kinetics was determined over 42 days. Rats that underwent 21-G needle puncture at rat tail discs were injected with rhGDF-5/PLGA microspheres at four weeks after needle injury. At eight weeks after the injection, disc height, glycosaminoglycans content, and DNA content of the discs were evaluated. In addition, gene expression analysis of aggrecan, collagen type I, and collagen type II in the rat nucleus pulposus was measured by real-time polymerase chain reaction. Rat discs were also assessed by histology using hematoxylin and eosin stain.
  
  
  
  Encapsulation of rhGDF-5 in PLGA microspheres guaranteed a sustained release of active rhGDF-5 for more than 42 days. The injection of GDF-5/PLGA microspheres resulted in a statistically significant restoration of disc height (p < 0.01), improvement of sulfated glycosaminoglycan (p < 0.05), DNA content (p < 0.05), and significantly increased mRNA levels of collagen type II (p < 0.01), and the differentiation index (the ratio of collagen type II to collagen type I, p < 0.01). In addition, rhGDF-5/PLGA microspheres treatment also improved histological changes induced by needle puncture.
  
  
  
  The results of this study suggest that injection of rhGDF-5 loaded in PLGA microspheres into rat tail discs may be as a promising therapy strategy to regenerate or repair the degenerative disc.
authors: Department of Histology and Embryology, School of Basic Medical Sciences, Capital Medical University, Beijing, China.
authors: Jihong
authors: J
authors: Yan
authors: Department of Histology and Embryology, School of Basic Medical Sciences, Capital Medical University, Beijing, China.
authors: Shu
authors: S
authors: Yang
authors: Department of Histology and Embryology, School of Basic Medical Sciences, Capital Medical University, Beijing, China.
authors: Huaimei
authors: H
authors: Sun
authors: Department of Histology and Embryology, School of Basic Medical Sciences, Capital Medical University, Beijing, China.
authors: Duo
authors: D
authors: Guo
authors: Department of Histology and Embryology, School of Basic Medical Sciences, Capital Medical University, Beijing, China.
authors: Bo
authors: B
authors: Wu
authors: Department of Histology and Embryology, School of Basic Medical Sciences, Capital Medical University, Beijing, China.
authors: Fengqing
authors: F
authors: Ji
authors: Department of Histology and Embryology, School of Basic Medical Sciences, Capital Medical University, Beijing, China ccmu2008@163.com.
authors: Deshan
authors: D
authors: Zhou
mesh_terms: D053674:Aggrecans / Q000235:genetics; D000818:Animals; D001672:Biocompatible Materials; D003094:Collagen / Q000235:genetics; D003692:Delayed-Action Preparations; D004195:Disease Models, Animal; D016503:Drug Delivery Systems; D055428:Growth Differentiation Factor 5 / Q000008:administration & dosage* / Q000493:pharmacokinetics; D006801:Humans; D055959:Intervertebral Disc Degeneration / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D019344:Lactic Acid; D008297:Male; D008422:Materials Testing; D008863:Microspheres; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000493:pharmacokinetics
chemical_list: D053674:Aggrecans; D001672:Biocompatible Materials; D003692:Delayed-Action Preparations; C525893:GDF5 protein, human; D055428:Growth Differentiation Factor 5; D012333:RNA, Messenger; D011994:Recombinant Proteins; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D003094:Collagen
keywords: Poly(lactic-co-glycolic acid) microspheres; annulus fibrosus; human growth and differentiation factor-5; intervertebral disc degeneration; nucleus pulposus