title: Intra-articular therapy with recombinant human GDF5 arrests disease progression and stimulates cartilage repair in the rat medial meniscus transection (MMT) model of osteoarthritis.
abstract: Investigation of osteoarthritis (OA) risk alleles suggests that reduced levels of growth and differentiation factor-5 (GDF5) may be a precipitating factor in OA. We hypothesized that intra-articular recombinant human GDF5 (rhGDF5) supplementation to the OA joint may alter disease progression.
  
  
  
  A rat medial meniscus transection (MMT) joint instability OA model was used. Animals received either one intra-articular injection, or two or three bi-weekly intra-articular injections of either 30 μg or 100 μg of rhGDF5 beginning on day 21 post surgery after structural pathology had been established. Nine weeks after MMT surgery, joints were processed for histological analysis following staining with toluidine blue. Control groups received intra-articular vehicle injections, comprising a glycine-buffered trehalose solution. OA changes in the joint were evaluated using histopathological end points that were collected by a pathologist who was blinded to treatment.
  
  
  
  Intra-articular rhGDF5 supplementation reduced cartilage lesions on the medial tibial plateau in a dose-dependent manner when administered therapeutically to intercept OA disease progression. A single 100 μg rhGDF5 injection on day 21 slowed disease progression at day 63. A similar effect was achieved with two bi-weekly injections of 30 μg. Two bi-weekly injections of 100 μg or three bi-weekly injections of 30 μg stopped progression of cartilage lesions. Importantly, three biweekly injections of 100 μg rhGDF5 stimulated significant cartilage repair.
  
  
  
  Intra-articular rhGDF5 supplementation can prevent and even reverse OA disease progression in the rat MMT OA model. Collectively, these results support rhGDF5 supplementation as an intra-articular disease modifying OA therapy.
authors.affiliation: DePuy Synthes Mitek Sports Medicine, Raynham, MA, USA. Electronic address: wparrish@its.jnj.com.
authors.forename: W R
authors.initials: WR
authors.lastname: Parrish
authors.affiliation: DePuy Synthes Mitek Sports Medicine, Raynham, MA, USA. Electronic address: bbyers@its.jnj.com.
authors.forename: B A
authors.initials: BA
authors.lastname: Byers
authors.affiliation: Advanced Therapeutics and Regenerative Medicine, Johnson & Johnson, Somerville, NJ, USA. Electronic address: sudongling@yahoo.com.
authors.forename: D
authors.initials: D
authors.lastname: Su
authors.affiliation: Advanced Therapeutics and Regenerative Medicine, Johnson & Johnson, Somerville, NJ, USA. Electronic address: jeffrey@geesinconsulting.com.
authors.forename: J
authors.initials: J
authors.lastname: Geesin
authors.affiliation: Advanced Therapeutics and Regenerative Medicine, Johnson & Johnson, Somerville, NJ, USA. Electronic address: uherzberg@celgene.com.
authors.forename: U
authors.initials: U
authors.lastname: Herzberg
authors.affiliation: Advanced Therapeutics and Regenerative Medicine, Johnson & Johnson, Somerville, NJ, USA. Electronic address: scottawadsworth@comcast.net.
authors.forename: S
authors.initials: S
authors.lastname: Wadsworth
authors.affiliation: Bolder BioPATH, Boulder, CO, USA. Electronic address: Alison@bolderbiopath.com.
authors.forename: A
authors.initials: A
authors.lastname: Bendele
authors.affiliation: DePuy Synthes Mitek Sports Medicine, Raynham, MA, USA. Electronic address: bstory1@its.jnj.com.
authors.forename: B
authors.initials: B
authors.lastname: Story
mesh_terms: D000818:Animals; D002358:Cartilage, Articular / Q000187:drug effects* / Q000473:pathology; D004195:Disease Models, Animal; D018450:Disease Progression; D055428:Growth Differentiation Factor 5 / Q000494:pharmacology*; D006801:Humans; D007270:Injections, Intra-Articular; D007719:Knee Joint / Q000187:drug effects* / Q000473:pathology; D008297:Male; D008592:Menisci, Tibial / Q000187:drug effects* / Q000473:pathology / Q000601:surgery; D020370:Osteoarthritis, Knee; D051381:Rats; D011917:Rats, Inbred Lew; D011994:Recombinant Proteins / Q000494:pharmacology; D000070600:Tibial Meniscus Injuries
chemical_list: C525893:GDF5 protein, human; D055428:Growth Differentiation Factor 5; D011994:Recombinant Proteins
keywords: Cartilage repair; GDF5; Growth and differentiation factor; Intraarticular therapy; Medial meniscus transection; Osteoarthritis