Age-dependent increase of discoidin domain receptor 2 and matrix metalloproteinase 13 expression in temporomandibular joint cartilage of type IX and type XI collagen-deficient mice

Lam, Nancy P.; Li, Y.; Waldman, A.B.; Brussiau, J.; Lee, P.L.; Olsen, Bjørn R.; Xu, Lin

doi:10.1016/j.archoralbio.2006.10.014

Cited by 30 publications

(24 citation statements)

References 17 publications

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“…Future experiments will reveal if the observed early phenotype influences the function of the mature skeleton. In particular, it will be interesting to analyze whether double deficient mice develop a more severe osteoarthritis phenotype than that described for mice lacking only collagen IX (Fässler et al, 1994;Hu et al, 2006;Lam et al, 2007).…”

Section: Discussionmentioning

confidence: 98%

Ablation of collagen IX and COMP disrupts epiphyseal cartilage architecture

et al. 2008

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Section: Discussionmentioning

confidence: 98%

Ablation of collagen IX and COMP disrupts epiphyseal cartilage architecture

et al. 2008

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“…The experimental procedure for histology has been described in our previous study (24). Serial sections were cut at thickness of 6 µm.…”

Section: Methodsmentioning

confidence: 99%

Early-onset osteoarthritis of mouse temporomandibular joint induced by partial discectomy

Polur

Lim

et al. 2009

Osteoarthritis and Cartilage

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Summary Objective The objective of this study is to characterize mouse temporomandibular joint (TMJ) following partial discectomy, since there is no documentation of whether or not partial discectomy can induce early-onset osteoarthritis (OA) in mouse TMJ. Methods Partial discs of TMJ in mice were removed by microsurgery. Histology was performed to characterize articular cartilages from the TMJ of mice. The morphology of the articular cartilages was evaluated using a modified Mankin scoring system. Immunohistostaining was carried out to examine the expression of discoidin domain receptor 2 (Ddr2), a type II collagen receptor, matrix metalloproteinase 13 (Mmp-13), and Mmp-derived type II collagen fragments in the articular cartilage of condyles from the mouse TMJ. Results Articular cartilage degeneration was seen in the mouse TMJ post discectomy, including increased proteoglycan staining in the extracellular matrix at 4 weeks, the appearance of chondrocyte clusters at 8 weeks, reduced proteoglycan staining and fibrillation at 12 weeks and the loss of articular cartilage at 16 weeks. Increased immunostaining for Ddr2, Mmp-13, and Mmp-derived type II collagen fragments was detected. Conclusion Results indicate that partial discectomy induces early-onset OA in mouse TMJ and that increased expression of Mmp-13, likely due to the elevated expression of Ddr2, may be one of the factors responsible for the early-onset OA in mouse TMJ.

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“…In contrast, DDR2 is expressed specifically in stromal cells and regulates cell proliferation and controls remodeling of the ECM by influencing the expression and activity of several matrix metalloproteinases (MMPs). (23)(24)(25)(26)(27)(28)(29)(30) Mice lacking DDR1 or DDR2 are both smaller than their wild-type littermates, (31)(32)(33) but the defective organs seem to be different in the two genetic models. The majority of Ddr1 knockout females show multiple reproductive defects, whereas Ddr2 knockout mice exhibit shortening of long bones and irregular growth of flat bones, which have been attributed previously to reduced chondrocyte and fibroblast proliferation.…”

Section: Introductionmentioning

confidence: 99%

An essential role of discoidin domain receptor 2 (DDR2) in osteoblast differentiation and chondrocyte maturation via modulation of Runx2 activation

Zhang

et al. 2010

Journal of Bone and Mineral Research

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Discoidin domain receptor 2 (DDR2) belongs to receptor tyrosine kinase (RTK) family and is activated by collagen binding. Although the bone defects in Ddr2 null mice have been reported for a decade, the molecular mechanism remains unclear. This study sought to investigate the function and detailed mechanism of DDR2 in osteogenic and chondrogenic differentiation. Herein we found that in preosteoblastic cells, DDR2 activation was enhanced by osteogenic induction but was not paralleled with the alteration of DDR2 expression. Under differentiated condition, downregulation of endogenous DDR2 through specific shRNA dramatically repressed osteoblastic marker gene expression and osteogenic differentiation. Enforced expression of constitutively activated DDR2 increased the expression of bone markers in both undifferentiated and differentiated osteoblasts. Importantly, molecular evidence showed that DDR2 regulated the transactivity of Runx2, a master transcription factor involved in skeletal development, by modulating its phosphorylation. Analysis of candidate protein kinases indicated that extracellular signal-regulated kinase (ERK) activation is responsive to DDR2 signaling and involved in DDR2 regulation of Runx2 phosphorylation and transcriptional activity. Notably, a gain-of-function mutant of Runx2 with enhanced ERK-independent phosphorylation rescued the impaired osteogenic phenotypes observed in Ddr2-silenced cells, whereas a Runx2 mutant devoid of phosphorylation regulation by ERK inhibited DDR2 induction of osteogenesis. In addition, DDR2 facilitated Runx2 transactivation and type X collagen expression in hypertrophic chondrocytes. Thus this study reveals for the first time that DDR2 plays an essential role in osteoblast and chondrocyte differentiation. The mechanism disclosure may provide therapeutic targets for human genetic disorders caused by DDR2 deficiency. ß

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Age-dependent increase of discoidin domain receptor 2 and matrix metalloproteinase 13 expression in temporomandibular joint cartilage of type IX and type XI collagen-deficient mice

Cited by 30 publications

References 17 publications

Ablation of collagen IX and COMP disrupts epiphyseal cartilage architecture

Ablation of collagen IX and COMP disrupts epiphyseal cartilage architecture

Early-onset osteoarthritis of mouse temporomandibular joint induced by partial discectomy

An essential role of discoidin domain receptor 2 (DDR2) in osteoblast differentiation and chondrocyte maturation via modulation of Runx2 activation

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