PMID- 27851984
OWN - NLM
STAT- MEDLINE
DCOM- 20180226
LR  - 20180330
IS  - 1522-9653 (Electronic)
IS  - 1063-4584 (Linking)
VI  - 25
IP  - 4
DP  - 2017 Apr
TI  - Intra-articular therapy with recombinant human GDF5 arrests disease progression 
      and stimulates cartilage repair in the rat medial meniscus transection (MMT) 
      model of osteoarthritis.
PG  - 554-560
LID - S1063-4584(16)30389-2 [pii]
LID - 10.1016/j.joca.2016.11.002 [doi]
AB  - OBJECTIVE: 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. METHODS: 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 mug or 100 mug 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. RESULTS: 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 mug rhGDF5 injection on day 21 slowed disease 
      progression at day 63. A similar effect was achieved with two bi-weekly 
      injections of 30 mug. Two bi-weekly injections of 100 mug or three bi-weekly 
      injections of 30 mug stopped progression of cartilage lesions. Importantly, three 
      biweekly injections of 100 mug rhGDF5 stimulated significant cartilage repair. 
      CONCLUSIONS: 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.
CI  - Copyright (c) 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.
FAU - Parrish, W R
AU  - Parrish WR
AD  - DePuy Synthes Mitek Sports Medicine, Raynham, MA, USA. Electronic address: 
      wparrish@its.jnj.com.
FAU - Byers, B A
AU  - Byers BA
AD  - DePuy Synthes Mitek Sports Medicine, Raynham, MA, USA. Electronic address: 
      bbyers@its.jnj.com.
FAU - Su, D
AU  - Su D
AD  - Advanced Therapeutics and Regenerative Medicine, Johnson & Johnson, Somerville, 
      NJ, USA. Electronic address: sudongling@yahoo.com.
FAU - Geesin, J
AU  - Geesin J
AD  - Advanced Therapeutics and Regenerative Medicine, Johnson & Johnson, Somerville, 
      NJ, USA. Electronic address: jeffrey@geesinconsulting.com.
FAU - Herzberg, U
AU  - Herzberg U
AD  - Advanced Therapeutics and Regenerative Medicine, Johnson & Johnson, Somerville, 
      NJ, USA. Electronic address: uherzberg@celgene.com.
FAU - Wadsworth, S
AU  - Wadsworth S
AD  - Advanced Therapeutics and Regenerative Medicine, Johnson & Johnson, Somerville, 
      NJ, USA. Electronic address: scottawadsworth@comcast.net.
FAU - Bendele, A
AU  - Bendele A
AD  - Bolder BioPATH, Boulder, CO, USA. Electronic address: Alison@bolderbiopath.com.
FAU - Story, B
AU  - Story B
AD  - DePuy Synthes Mitek Sports Medicine, Raynham, MA, USA. Electronic address: 
      bstory1@its.jnj.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20161113
PL  - England
TA  - Osteoarthritis Cartilage
JT  - Osteoarthritis and cartilage
JID - 9305697
RN  - 0 (GDF5 protein, human)
RN  - 0 (Growth Differentiation Factor 5)
RN  - 0 (Recombinant Proteins)
SB  - IM
MH  - Animals
MH  - Cartilage, Articular/*drug effects/pathology
MH  - Disease Models, Animal
MH  - Disease Progression
MH  - Growth Differentiation Factor 5/*pharmacology
MH  - Humans
MH  - Injections, Intra-Articular
MH  - Knee Joint/*drug effects/pathology
MH  - Male
MH  - Menisci, Tibial/*drug effects/pathology/surgery
MH  - Osteoarthritis, Knee
MH  - Rats
MH  - Rats, Inbred Lew
MH  - Recombinant Proteins/pharmacology
MH  - Tibial Meniscus Injuries
OTO - NOTNLM
OT  - Cartilage repair
OT  - GDF5
OT  - Growth and differentiation factor
OT  - Intraarticular therapy
OT  - Medial meniscus transection
OT  - Osteoarthritis
EDAT- 2016/11/17 06:00
MHDA- 2018/02/27 06:00
CRDT- 2016/11/17 06:00
PHST- 2016/06/02 00:00 [received]
PHST- 2016/09/23 00:00 [revised]
PHST- 2016/11/02 00:00 [accepted]
PHST- 2016/11/17 06:00 [pubmed]
PHST- 2018/02/27 06:00 [medline]
PHST- 2016/11/17 06:00 [entrez]
AID - S1063-4584(16)30389-2 [pii]
AID - 10.1016/j.joca.2016.11.002 [doi]
PST - ppublish
SO  - Osteoarthritis Cartilage. 2017 Apr;25(4):554-560. doi: 
      10.1016/j.joca.2016.11.002. Epub 2016 Nov 13.