TMJ degeneration in SAMP8 mice is accompanied by deranged Ihh signaling.
The temporomandibular joint (TMJ) functions as a load-bearing diarthrodial joint during mastication, and its continuous use and stress can lead to degeneration over age. Using senescence-accelerated (SAMP8) mice that develop early osteoarthritis-like changes in synovial joints at high frequency, we analyzed possible molecular mechanisms of TMJ degeneration and tested whether and how malocclusion may accelerate it. Condylar articular cartilage in young SAMP8 mice displayed early-onset osteoarthritic changes that included reductions in superficial/chondroprogenitor cell number, proteoglycan/collagen content, and Indian hedgehog (Ihh)-expressing chondrocytes. Following malocclusion induced by tooth milling, the SAMP8 condyles became morphologically defective, displayed even lower proteoglycan levels, and underwent abnormal chondrocyte maturation compared with malocclusion-treated condyles in wild-type mice. Malocclusion also induced faster progression of pathologic changes with increasing age in SAMP8 condyles as indicated by decreased PCNA-positive proliferating chondroprogenitors and increased TUNEL-positive apoptotic cells. These changes were accompanied by steeper reductions in Ihh signaling and by expression of matrix metalloproteinase 13 at the chondro-osseous junction in SAMP8 articular cartilage. In sum, we show for the first time that precocious TMJ degeneration in SAMP8 mice is accompanied by--and possibly attributable to--altered Ihh signaling and that occlusal dysfunction accelerates progression toward degenerative TMJ disease in this model.
Department of Periodontology, Tokyo Dental College, Tokyo, Japan.
Y
Y
Ishizuka
Y
Y
Shibukawa
M
M
Nagayama
R
R
Decker
T
T
Kinumatsu
A
A
Saito
M
M
Pacifici
E
E
Koyama
D000367:Age Factors; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D002352:Carrier Proteins / Q000032:analysis; D002358:Cartilage, Articular / Q000473:pathology; D019902:Chondrocytes / Q000473:pathology; D003094:Collagen / Q000032:analysis; D024042:Collagen Type I / Q000032:analysis; D024043:Collagen Type II / Q000032:analysis; D024121:Collagen Type X / Q000032:analysis; D004195:Disease Models, Animal; D018450:Disease Progression; D053823:Hedgehog Proteins / Q000032:analysis*; D051741:Kruppel-Like Transcription Factors / Q000032:analysis; D008310:Malocclusion / Q000150:complications; D008335:Mandibular Condyle / Q000473:pathology; D053509:Matrix Metalloproteinase 13 / Q000032:analysis; D008562:Membrane Glycoproteins / Q000032:analysis; D051379:Mice; D008815:Mice, Inbred Strains; D010003:Osteoarthritis / Q000378:metabolism*; D000072079:Patched Receptors; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D011509:Proteoglycans / Q000032:analysis; D011956:Receptors, Cell Surface / Q000032:analysis; D015398:Signal Transduction / Q000502:physiology*; D013234:Stem Cells / Q000473:pathology; D013705:Temporomandibular Joint Disorders / Q000378:metabolism*; D000071676:Zinc Finger Protein GLI1; D000075746:Zinc Finger Protein Gli2
D002352:Carrier Proteins; D024042:Collagen Type I; D024043:Collagen Type II; D024121:Collagen Type X; C498520:Gli1 protein, mouse; C000618551:Gli2 protein, mouse; D053823:Hedgehog Proteins; C498447:Hhip protein, mouse; D051741:Kruppel-Like Transcription Factors; D008562:Membrane Glycoproteins; D000072079:Patched Receptors; D018809:Proliferating Cell Nuclear Antigen; D011509:Proteoglycans; D011956:Receptors, Cell Surface; D000071676:Zinc Finger Protein GLI1; D000075746:Zinc Finger Protein Gli2; C514061:ihh protein, mouse; D003094:Collagen; D053509:Matrix Metalloproteinase 13; C507081:Mmp13 protein, mouse
Indian hedgehog; degenerative joint disease; osteoarthritis; senescence-accelerated mouse; superficial cell; temporomandibular joint