Indian hedgehog roles in post-natal TMJ development and organization.
Indian hedgehog (Ihh) is essential for embryonic mandibular condylar growth and disc primordium formation. To determine whether it regulates those processes during post-natal life, we ablated Ihh in cartilage of neonatal mice and assessed the consequences on temporomandibular joint (TMJ) growth and organization over age. Ihh deficiency caused condylar disorganization and growth retardation and reduced polymorphic cell layer proliferation. Expression of Sox9, Runx2, and Osterix was low, as was that of collagen II, collagen I, and aggrecan, thus altering the fibrocartilaginous nature of the condyle. Though a disc formed, it exhibited morphological defects, partial fusion with the glenoid bone surface, reduced synovial cavity space, and, unexpectedly, higher lubricin expression. Analysis of the data shows, for the first time, that continuous Ihh action is required for completion of post-natal TMJ growth and organization. Lubricin overexpression in mutants may represent a compensatory response to sustain TMJ movement and function.
Ochiai
T
T
Department of Orthopaedic Surgery, Thomas Jefferson University College of Medicine, 1015 Walnut Street, Curtis Building Room 501, Philadelphia, PA 19107, USA.
Shibukawa
Y
Y
Nagayama
M
M
Mundy
C
C
Yasuda
T
T
Okabe
T
T
Shimono
K
K
Kanyama
M
M
Hasegawa
H
H
Maeda
Y
Y
Lanske
B
B
Pacifici
M
M
Koyama
E
E
D053674:Aggrecans / Q000096:biosynthesis / Q000235:genetics; D000818:Animals; D000844:Ankylosis / Q000235:genetics / Q000378:metabolism; D002358:Cartilage, Articular / Q000033:anatomy & histology / Q000254:growth & development*; D019902:Chondrocytes / Q000473:pathology; D024043:Collagen Type II / Q000096:biosynthesis / Q000235:genetics; D050659:Core Binding Factor Alpha 1 Subunit / Q000096:biosynthesis / Q000235:genetics; D015536:Down-Regulation; D051445:Fibrocartilage / Q000033:anatomy & histology / Q000254:growth & development; D006132:Growth Plate / Q000002:abnormalities; D053823:Hedgehog Proteins / Q000235:genetics / Q000502:physiology*; D008335:Mandibular Condyle / Q000033:anatomy & histology / Q000254:growth & development*; D051379:Mice; D018345:Mice, Knockout; D011509:Proteoglycans / Q000096:biosynthesis; D055758:SOX9 Transcription Factor / Q000096:biosynthesis / Q000235:genetics; D000076182:Sp7 Transcription Factor; D013704:Temporomandibular Joint / Q000033:anatomy & histology* / Q000254:growth & development*; D019224:Temporomandibular Joint Disc / Q000033:anatomy & histology / Q000254:growth & development; D013705:Temporomandibular Joint Disorders / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics; D000099158:Proteoglycan 4
D053674:Aggrecans; D024043:Collagen Type II; D050659:Core Binding Factor Alpha 1 Subunit; D053823:Hedgehog Proteins; D011509:Proteoglycans; D055758:SOX9 Transcription Factor; D000076182:Sp7 Transcription Factor; D014157:Transcription Factors; C498837:Prg4 protein, mouse; D000099158:Proteoglycan 4; C493716:Runx2 protein, mouse; C527933:Sox9 protein, mouse; C479466:Sp7 protein, mouse; C514061:ihh protein, mouse