PMID- 16947423
OWN - NLM
STAT- MEDLINE
DCOM- 20061108
LR  - 20161124
IS  - 0004-3591 (Print)
IS  - 0004-3591 (Linking)
VI  - 54
IP  - 9
DP  - 2006 Sep
TI  - Pathogenesis of osteoarthritis-like changes in the joints of mice deficient in 
      type IX collagen.
PG  - 2891-900
AB  - OBJECTIVE: To examine the pathogenetic mechanisms of osteoarthritis (OA)-like 
      changes in Col9a1-/- mice, which are deficient in type IX collagen. METHODS: Knee 
      joints and temporomandibular joints (TMJs) from Col9a1-/- mice and their 
      wild-type (Col9a1+/+) littermates were examined by light microscopy. 
      Immunohistochemical staining was performed to examine the expression of matrix 
      metalloproteinase 3 (MMP-3) and MMP-13, degraded type II collagen, and the 
      discoidin domain receptor 2 (DDR-2) in knee joints. Cartilage mechanics were also 
      evaluated for compressive properties by microindentation testing of the tibial 
      plateau and for tensile properties by osmotic loading of the femoral condyle. 
      RESULTS: Histologic analysis showed age-dependent OA-like changes in the knee and 
      TMJs of Col9a1-/- mice starting at the age of 3 months. At the age of 6 months, 
      enhanced proteoglycan degradation was observed in the articular cartilage of the 
      knee and TMJs of the mutant mice. The expression of MMP-13 and DDR-2 protein and 
      the amount of degraded type II collagen were higher in the knee joints of 
      Col9a1-/- mice than in their wild-type littermates at the age of 6 months. 
      Changes in cartilage mechanics were observed in the femoral and tibial plateaus 
      of Col9a1-/- mice at 6 months, including a decrease in the compressive modulus 
      and uniaxial modulus. At 3 and 6 months of age, tibial cartilage in Col9a1-/- 
      mice was found to be more permeable to fluid flow, with an associated compromise 
      in the fluid pressurization mechanism of load support. All of these changes 
      occurred only at medial sites. CONCLUSION: Lack of type IX collagen in Col9a1-/- 
      mice results in age-dependent OA-like changes in the knee joints and TMJs.
FAU - Hu, K
AU  - Hu K
AD  - Harvard School of Dental Medicine, Boston, Massachusetts 02115, USA.
FAU - Xu, L
AU  - Xu L
FAU - Cao, L
AU  - Cao L
FAU - Flahiff, C M
AU  - Flahiff CM
FAU - Brussiau, J
AU  - Brussiau J
FAU - Ho, K
AU  - Ho K
FAU - Setton, L A
AU  - Setton LA
FAU - Youn, I
AU  - Youn I
FAU - Guilak, F
AU  - Guilak F
FAU - Olsen, B R
AU  - Olsen BR
FAU - Li, Y
AU  - Li Y
LA  - eng
GR  - P01-AR-050245/AR/NIAMS NIH HHS/United States
GR  - R01-AR-36819/AR/NIAMS NIH HHS/United States
GR  - R03-AR-05001/AR/NIAMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PL  - United States
TA  - Arthritis Rheum
JT  - Arthritis and rheumatism
JID - 0370605
RN  - 0 (Collagen Type IX)
RN  - 0 (Receptors, Mitogen)
RN  - EC 2.7.10.1 (Discoidin Domain Receptors)
RN  - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases)
RN  - EC 3.4.24.- (Collagenases)
RN  - EC 3.4.24.- (Matrix Metalloproteinase 13)
RN  - EC 3.4.24.- (Mmp13 protein, mouse)
RN  - EC 3.4.24.17 (Matrix Metalloproteinase 3)
SB  - IM
MH  - Animals
MH  - Collagen Type IX/*deficiency/genetics
MH  - Collagenases/metabolism
MH  - Discoidin Domain Receptors
MH  - Disease Models, Animal
MH  - Joints/metabolism/*pathology
MH  - Matrix Metalloproteinase 13
MH  - Matrix Metalloproteinase 3/metabolism
MH  - Mice
MH  - Mice, Knockout
MH  - Osteoarthritis/*genetics/*pathology
MH  - Receptor Protein-Tyrosine Kinases/metabolism
MH  - Receptors, Mitogen/metabolism
EDAT- 2006/09/02 09:00
MHDA- 2006/11/10 09:00
CRDT- 2006/09/02 09:00
PHST- 2006/09/02 09:00 [pubmed]
PHST- 2006/11/10 09:00 [medline]
PHST- 2006/09/02 09:00 [entrez]
AID - 10.1002/art.22040 [doi]
PST - ppublish
SO  - Arthritis Rheum. 2006 Sep;54(9):2891-900. doi: 10.1002/art.22040.