Indian Hedgehog Roles in Post-natal TMJ Development and Organization

Ochiai, Takanaga; Shibukawa, Yoshihiro; Nagayama, Motohiko; Mundy, Christina; Yasuda, Tadashi; Okabe, Takahiro; Shimono, Kengo; Kanyama, Manabu; Hasegawa, Hiromasa; Maeda, Yukiko; Lanske, Beate; Pacifici, Maurizio; Koyama, Eiki

doi:10.1177/0022034510363078

Cited by 66 publications

(75 citation statements)

References 37 publications

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“…We found that Col2-cyan ( fig. 4 ) was localized to the flattened/hypertrophic zones and absent from the upper zones of the mandibular condylar cartilage, which correlated with previous reports on Col2a1 mRNA endogenous gene expression [Shibukawa et al, 2007;Ochiai et al, 2010] in the mandibular condylar cartilage. Gene expression analysis of freshly isolated Col2-cyan cells further supported the expression of Col2-cyan in the flattened/hypertrophic zones.…”

Section: Discussionsupporting

confidence: 90%

Isolation and Characterization of Murine Mandibular Condylar Cartilage Cell Populations

Chen¹,

Utreja

Kalajzić³

et al. 2011

Cells Tissues Organs

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containing the Col3.6-cre recombinase were bred with cre reporter mice. Results: Localization and analysis of gene expression revealed that Col3.6-tpz-positive cells corresponded to the polymorphic/flattened zones and Col2-cyan-positive cells corresponded to the flattened/hypertrophic zones of the mandibular condylar cartilage. Mandibular condylar cartilage FACS-sorted Col3.6-tpz-positive cells have the potential to differentiate into bone, cartilage, and fat. Cell fate mapping revealed that Col3.6 cells are precursors of some of the hypertrophic chondrocytes in the mandibular condylar cartilage. Conclusion: Col3.6-tpz cells represent an earlier stage of the mandibular condylar cartilage maturation pathway. Abstract Objectives:The mandibular condylar cartilage is a heterogeneous tissue containing cells at various stages of chondrocyte maturation organized into 4 zones: superficial, polymorphic, flattened, and hypertrophic. The goal of this study was to use transgenic mice containing chondrocyte maturation markers fused to fluorescent protein transgenes to isolate and characterize homogenous cell populations of the mandibular condylar cartilage. Methods: Fluorescent reporter expression in the mandibular condylar cartilage of transgenic mice containing the 3.6-kb fragment of the rat collagen type 1 promoter fused to a topaz-fluorescent protein (Col3.6-tpz), collagen type 2 promoter fused to a cyanfluorescent protein (Col2-cyan), and/or collagen type 10 promoter fused to cherry-fluorescent protein (Col10-cherry) was examined. Mandibular condylar cartilage cells were analyzed by fluorescence-activated cell sorting (FACS) and either used for gene expression analysis or plated in cell cultures and exposed to adipogenic, osteogenic, or chondrogenic conditions. To determine cell fate, transgenic mice Accepted after revision:

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Section: Discussionsupporting

confidence: 90%

Isolation and Characterization of Murine Mandibular Condylar Cartilage Cell Populations

Chen¹,

Utreja

Kalajzić³

et al. 2011

Cells Tissues Organs

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“…The observation that genetic inactivation of the indian hedgehog (IHH) pathway conveys resistance to degenerative arthritis might be explained by a reduction in the mineral apposition rate of fibrocartilage and articular cartilage 38, 39 or a suppression of the development of osteophytes 40 within the expanded regions of fibrocartilage. That IHH is required for normal formation and maintenance of the chondral fibrocartilage of the TMJ 41, 42 supports this concept. In fact, IHH may be upstream of subsequent cartilage degradation as IHH’s regulation of RUNX2 can lead to increased expression of ADAMTS5, a major protease found in OA cartilage 39 .…”

Section: Discussionmentioning

confidence: 76%

Response of knee fibrocartilage to joint destabilization

Dyment

Hagiwara

Jiang

et al. 2015

Osteoarthritis and Cartilage

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Objective A major challenge to understanding osteoarthritis pathology is identifying the cellular events that precede the onset of cartilage damage. The objective of this study is to determine the effect of joint destabilization on early changes to fibrocartilage in the joint. Design/Methods The anterior cruciate ligament was transected in collagen reporter mice (Col1GFP and ColXRFP). Mineralization labels were given every two weeks to measure new mineralized cartilage apposition. Novel fluorescent histology of mineralized tissue was used to characterize the changes in fibrocartilage at 2 and 4 weeks post-injury. Results Changes in fibrocartilaginous structures of the joint occur as early as two weeks after injury and are well developed by four weeks. The alterations are seen in multiple entheses and in the medial surface of the femoral and tibial condyles. In the responding entheses, mineral apposition towards the ligament midsubstance results in thickening of the mineralize fibrocartilage. These changes are associated with increases in ColX-RFP, Col1-CFP reporter activity and alkaline phosphatase enzyme activity. Mineral apposition also occurs in the fibrocartilage of the non-articular regions of the medial condyles by 2 weeks and develops into osteophytes by 4 weeks post-injury. An unexpected observation is punctate expression of tartrate resistant acid phosphatase activity in unmineralized fibrochondrocytes adjacent to active appositional mineralization. Discussion These observations suggest that fibrocartilage activates prior to degradation of the articular cartilage. Thus clinical and histological imaging of fibrocartilage may be an earlier indicator of disease initiation and may indicate a more appropriate time to start preventative treatment.

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“…19,20 Condylar disorganization, growth retardation, reduced polymorphic cell layer proliferation, and low expression of COL2A1, COL1A1, and SOX9 were found in Ihh-deficient mice from postnatal TMJ. 33 Previous study demonstrated that Ihh acts as a mediator of mechanotransduction, which converts mechanical signals to stimulate cellular proliferation in the condylar cartilage. 34 The high expression of Ihh can also stimulate chondrocyte secretion of PTHrP effectively.…”

Section: Discussionmentioning

confidence: 99%