Mice deficient in biglycan and fibromodulin as a model for temporomandibular joint osteoarthritis.
The temporomandibular joint (TMJ) within the craniofacial complex is unique. In humans, the TMJ can become diseased resulting in severe and disabling pain. There are no cures for TMJ disease at this time. Animal models of TMJ disease are scarce, but some exist, and they are described in this paper. We present in greater detail one animal model that is deficient in two extracellular matrix (ECM) proteoglycans, biglycan (BGN) and fibromodulin (FMOD). Doubly deficient BGN/FMOD mice develop premature TMJ osteoarthritis (OA). In order to explore the mechanistic basis of TMJ-OA, tissues from the condyle of mutant mice were examined for their relative capacity to differentiate and undergo apoptosis. Our data show that there is a redistribution of the critical ECM protein, type II collagen, in mutant mice compared with controls. Mutant mice also have increased apoptosis of the chondrocytes embedded in the articular cartilage. We speculate that the overall imbalance in apoptosis may be the cellular basis for the abnormal production of structural ECM proteins. The abnormal production of the ECM could, in turn, lead to premature erosion and degradation of the articular surface resulting in TMJ-OA. These data underscore the importance of the ECM in controlling the structural integrity of the TMJ.
Wadhwa
Sunil
S
Craniofacial and Skeletal Diseases Branch, National Institutes of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA. wadhwa@uchc.edu
Embree
Mildred
M
Ameye
Laurent
L
Young
Marian F
MF
D000818:Animals; D017209:Apoptosis; D058578:Biglycan; D024043:Collagen Type II / Q000378:metabolism; D004195:Disease Models, Animal; D016326:Extracellular Matrix Proteins / Q000172:deficiency* / Q000235:genetics; D000071235:Fibromodulin; D008335:Mandibular Condyle / Q000473:pathology; D051379:Mice / Q000235:genetics* / Q000378:metabolism; D018345:Mice, Knockout; D010003:Osteoarthritis / Q000235:genetics / Q000473:pathology*; D020370:Osteoarthritis, Knee / Q000473:pathology; D011509:Proteoglycans / Q000172:deficiency* / Q000235:genetics; D013704:Temporomandibular Joint / Q000473:pathology*; D013705:Temporomandibular Joint Disorders / Q000235:genetics / Q000473:pathology*
C546884:BGN protein, human; C546885:Bgn protein, mouse; D058578:Biglycan; D024043:Collagen Type II; D016326:Extracellular Matrix Proteins; C000604330:FMOD protein, human; C000604332:Fmod protein, mouse; D011509:Proteoglycans; D000071235:Fibromodulin