PMID- 18050203
OWN - NLM
STAT- MEDLINE
DCOM- 20080207
LR  - 20220330
IS  - 0004-3591 (Print)
IS  - 0004-3591 (Linking)
VI  - 56
IP  - 12
DP  - 2007 Dec
TI  - Articular cartilage and biomechanical properties of the long bones in 
      Frzb-knockout mice.
PG  - 4095-103
AB  - OBJECTIVE: Ligands and antagonists of the WNT pathway are linked to osteoporosis 
      and osteoarthritis. In particular, polymorphisms in the FRZB gene, a secreted WNT 
      antagonist, have been associated with osteoarthritis. The aim of this study was 
      to examine cartilage and bone in Frzb(-/-) mice. METHODS: The Frzb gene in mice 
      was inactivated using a Cre/loxP strategy. Three models of osteoarthritis were 
      used: collagenase, papain, and methylated bovine serum albumin induced. Bone 
      biology was studied using density measurements and microfocal computed 
      tomography. Bone stiffness and mechanical loading-induced bone adaptation were 
      studied by compression of the ulnae. RESULTS: Targeted deletion of the Frzb gene 
      in mice increased articular cartilage loss during arthritis triggered by 
      instability, enzymatic injury, or inflammation. Cartilage damage in Frzb(-/-) 
      mice was associated with increased WNT signaling and matrix metalloproteinase 3 
      (MMP-3) expression and activity. Frzb(-/-) mice had increased cortical bone 
      thickness and density, resulting in stiffer bones, as demonstrated by 
      stress-strain relationship analyses. Moreover, Frzb(-/-) mice had an increased 
      periosteal anabolic response to mechanical loading as compared with wild-type 
      mice. CONCLUSION: The genetic association between osteoarthritis and FRZB 
      polymorphisms is corroborated by increased cartilage proteoglycan loss in 3 
      different models of arthritis in Frzb(-/-) mice. Loss of Frzb may contribute to 
      cartilage damage by increasing the expression and activity of MMPs, in a 
      WNT-dependent and WNT-independent manner. FRZB deficiency also resulted in 
      thicker cortical bone, with increased stiffness and higher cortical appositional 
      bone formation after loading. This may contribute to the development of 
      osteoarthritis by producing increased strain on the articular cartilage during 
      normal locomotion but may protect against osteoporotic fractures.
FAU - Lories, Rik J U
AU  - Lories RJ
AD  - Laboratory for Skeletal Development and Joint Disorders, Department of 
      Rheumatology, University Hospitals Leuven, Katholieke Universiteit Leuven, 
      Herestraat 49, Leuven, Belgium.
FAU - Peeters, Jenny
AU  - Peeters J
FAU - Bakker, Astrid
AU  - Bakker A
FAU - Tylzanowski, Przemko
AU  - Tylzanowski P
FAU - Derese, Inge
AU  - Derese I
FAU - Schrooten, Jan
AU  - Schrooten J
FAU - Thomas, J Terrig
AU  - Thomas JT
FAU - Luyten, Frank P
AU  - Luyten FP
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 (Glycoproteins)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (WD repeat containing planar cell polarity effector)
RN  - 0 (Wnt Proteins)
RN  - EC 3.4.22.2 (Papain)
RN  - EC 3.4.24.- (Collagenases)
RN  - EC 3.4.24.17 (Matrix Metalloproteinase 3)
SB  - IM
CIN - Arthritis Rheum. 2007 Dec;56(12):3881-3. PMID: 18050212
MH  - Animals
MH  - Biomechanical Phenomena
MH  - Bone Density/physiology
MH  - Cartilage Diseases/metabolism/pathology
MH  - Cartilage, Articular/*metabolism/pathology
MH  - Collagenases
MH  - Disease Models, Animal
MH  - Femur/*metabolism/pathology
MH  - Glycoproteins/genetics/*metabolism
MH  - Homeostasis/physiology
MH  - Intracellular Signaling Peptides and Proteins
MH  - Matrix Metalloproteinase 3/*metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Osteoarthritis/chemically induced/*metabolism/pathology
MH  - Osteoporosis/metabolism/pathology
MH  - Papain
MH  - Tibia/*metabolism/pathology
MH  - Wnt Proteins/*metabolism
EDAT- 2007/12/01 09:00
MHDA- 2008/02/08 09:00
CRDT- 2007/12/01 09:00
PHST- 2007/12/01 09:00 [pubmed]
PHST- 2008/02/08 09:00 [medline]
PHST- 2007/12/01 09:00 [entrez]
AID - 10.1002/art.23137 [doi]
PST - ppublish
SO  - Arthritis Rheum. 2007 Dec;56(12):4095-103. doi: 10.1002/art.23137.