PMID- 18163499
OWN - NLM
STAT- MEDLINE
DCOM- 20080310
LR  - 20161124
IS  - 0004-3591 (Print)
IS  - 0004-3591 (Linking)
VI  - 58
IP  - 1
DP  - 2008 Jan
TI  - Association of microsomal prostaglandin E synthase 1 deficiency with impaired 
      fracture healing, but not with bone loss or osteoarthritis, in mouse models of 
      skeletal disorders.
PG  - 172-83
LID - 10.1002/art.23158 [doi]
AB  - OBJECTIVE: Prostaglandin E synthase (PGES) functions as the terminal enzyme in 
      the biosynthesis of prostaglandin E(2) (PGE(2)) and is a potent regulator of bone 
      and cartilage metabolism. Among the 3 isozymes of PGES, microsomal PGES-1 
      (mPGES-1) is known to play the most critical role in the production of PGE(2) in 
      pathophysiologic events. This study investigated the roles of mPGES-1 under 
      normal physiologic and pathophysiologic conditions in the skeletons of 
      mPGES-1-deficient (mPGES-1(-/-)) mice. METHODS: Skeletons of mPGES-1(-/-) mice 
      and their wild-type littermates were compared by radiologic and histologic 
      analyses. Four models of skeletal disorders were created: bone loss induced by 
      ovariectomy, bone loss induced by hind limb unloading, osteoarthritis (OA) 
      induced by instability in the knee joint, and bone fracture by osteotomy at the 
      tibial midshaft. Expression of the PGES enzymes was examined by 
      immunohistochemistry and real-time reverse transcription-polymerase chain 
      reaction. The cellular mechanism of fracture healing was examined in ex vivo 
      cultures of costal cartilage chondrocytes. RESULTS: Microsomal PGES-1(-/-) mice 
      had unaffected skeletal phenotypes under normal physiologic conditions. In the 
      bone fracture model, fracture healing was impaired by the mPGES-1 deficiency, 
      with half of the mice remaining in a non-bone union state even after 21 days; 
      normal fracture healing was restored by adenoviral reintroduction of mPGES-1. The 
      other skeletal disorders were not affected by the mPGES-1 deficiency. In vivo and 
      ex vivo analyses revealed an impaired proliferation of chondrocytes in cartilage 
      with the mPGES-1 deficiency, at an early stage of fracture healing. CONCLUSION: 
      In these mouse models of skeletal disorders, mPGES-1 was indispensable for bone 
      repair through chondrocyte proliferation, but was not essential for the skeleton 
      under normal physiologic conditions, nor did it play a role in the 
      pathophysiologic conditions of bone loss due to ovariectomy, bone loss due to 
      unloading, or stress-induced OA.
FAU - Yamakawa, Kiyofumi
AU  - Yamakawa K
AD  - University of Tokyo, Tokyo, Japan.
FAU - Kamekura, Satoru
AU  - Kamekura S
FAU - Kawamura, Naohiro
AU  - Kawamura N
FAU - Saegusa, Masatomo
AU  - Saegusa M
FAU - Kamei, Daisuke
AU  - Kamei D
FAU - Murakami, Makoto
AU  - Murakami M
FAU - Kudo, Ichiro
AU  - Kudo I
FAU - Uematsu, Satoshi
AU  - Uematsu S
FAU - Akira, Shizuo
AU  - Akira S
FAU - Chung, Ung-il
AU  - Chung UI
FAU - Nakamura, Kozo
AU  - Nakamura K
FAU - Kawaguchi, Hiroshi
AU  - Kawaguchi H
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Arthritis Rheum
JT  - Arthritis and rheumatism
JID - 0370605
RN  - 0 (Prostaglandins)
RN  - EC 5.3.- (Intramolecular Oxidoreductases)
RN  - EC 5.3.99.3 (Prostaglandin-E Synthases)
RN  - EC 5.3.99.3 (Ptges protein, mouse)
SB  - IM
MH  - Animals
MH  - Bone Diseases, Metabolic/diagnostic imaging/metabolism/*physiopathology
MH  - Chondrocytes/physiology
MH  - Disease Models, Animal
MH  - Fracture Healing/*physiology
MH  - Fractures, Bone/diagnostic imaging/metabolism/*physiopathology
MH  - Intramolecular Oxidoreductases/deficiency/*genetics
MH  - Joint Instability/diagnostic imaging/metabolism/physiopathology
MH  - Mice
MH  - Mice, Mutant Strains
MH  - Microsomes/enzymology
MH  - Osteoarthritis/diagnostic imaging/metabolism/*physiopathology
MH  - Ovariectomy
MH  - Phenotype
MH  - Prostaglandin-E Synthases
MH  - Prostaglandins/metabolism
MH  - Radiography
MH  - Weight-Bearing
EDAT- 2008/01/01 09:00
MHDA- 2008/03/11 09:00
CRDT- 2008/01/01 09:00
PHST- 2008/01/01 09:00 [pubmed]
PHST- 2008/03/11 09:00 [medline]
PHST- 2008/01/01 09:00 [entrez]
AID - 10.1002/art.23158 [doi]
PST - ppublish
SO  - Arthritis Rheum. 2008 Jan;58(1):172-83. doi: 10.1002/art.23158.