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DDR2 cartilage

Lauren B Manning, Yefu Li, Nithya S Chickmagalur, Xiaolong Li, Lin Xu
Osteoarthritis (OA) is the most common form of arthritis disorders, but the identification of therapeutic targets to effectively prevent OA has been increasingly difficult. The goal of this investigation is to provide experimental evidence that discoidin domain receptor 2 (DDR2) may be an ideal target for the development of disease-modifying OA drugs. Ddr2 was conditionally deleted from articular cartilage of adult mouse knee joints. Aggrecan-CreERT2;floxed Ddr2 mice, which were generated by crossing Aggrecan-CreERT2 mice with floxed Ddr2 mice, then received tamoxifen injections at the age of 8 weeks...
September 15, 2016: American Journal of Pathology
Siim Suutre, Irina Kerna, Mare Lintrop, Hannes Tamm, Marina Aunapuu, Andres Arend, Agu Tamm
OBJECTIVE: To determine, if staining of articular cartilage for proteoglycans (natural element of healthy and functioning cartilage) and discoidin domain receptor 2 (DDR2) (a protein associated with articular cartilage degradation) is correlated with histological tissue damage or radiographic assessment score in patients with early stages of knee osteoarthritis (OA). METHOD: 40 patients, with early stage OA were enrolled, from whom the biopsies for histological and immunohistochemical studies were obtained from edge of the femoral condyle during the arthroscopy...
2015: International Journal of Clinical and Experimental Pathology
Li Nianhu, Xia Lei, Yi Sheng, Yu Jianhui, Zhai Yi, Xu Zhanwang
OBJECTIVE: To determine the effects of Bushenhuoxue formula (BHF) on interleukin-1 beta (IL-1β), transforming growth factor beta 1 (TGF-β1), discoidin domain receptor 2 (DDR2) and matrix metalloproteinase-1 (MMP-1) levels in a rat model of osteoarthritis (OA). METHODS: Sprague-Dawley rats were used to establish an OA model and subjected to various treatments over 6 weeks. Rats were treated with BHF, glucosamine sulfate (GS), or starch as a control. Serum levels of IL-1β and MMP-1 and joint fluid levels of IL-1β were determined by means of ELISAs...
April 2015: Journal of Traditional Chinese Medicine, Chung i Tsa Chih Ying Wen Pan
Shun-Cheng Wu, Hsu-Feng Hsiao, Mei-Ling Ho, Yung-Li Hung, Je-Ken Chang, Gwo-Jaw Wang, Chau-Zen Wang
Effectively directing the chondrogenesis of adipose-derived stem cells (ADSCs) to engineer articular cartilage represents an important challenge in ADSC-based articular cartilage tissue engineering. The discoidin domain receptor 1 (DDR1) has been shown to affect cartilage homeostasis; however, little is known about the roles of DDR1 in ADSC chondrogenesis. In this study, we used the three-dimensional culture pellet culture model system with chondrogenic induction to investigate the roles of DDR1 in the chondrogenic differentiation of human ADSCs (hADSCs)...
May 1, 2015: American Journal of Physiology. Cell Physiology
Sihan Zhang, Yu Zhong, Rongheng Li, Wei Wang, Li Zeng, Zheming Wang, Ping Jia, Rui Wu
The aim of the present study was to assess the association between chondrocytes and the extracellular matrix (ECM), and determine whether this contributes to osteoarthritis (OA). Chondrocyte hypertrophy was measured in articular cartilage samples from early-stage OA patients. In addition, rat chondrocytes were cultured and divided into four groups (A to D): Group A was an untreated control group, group B was incubated with chicken collagen II, group C was transfected with the discoidin domain of discoidin domain receptor-2 (DDR2) and group D was transfected with full‑length DDR2...
September 2014: Molecular Medicine Reports
Armando Salazar, Ilona Polur, Jacqueline M Servais, Yefu Li, Lin Xu
OBJECTIVE: To determine whether reduction of the discoidin domain receptor 2 (Ddr2) delays the progression of condylar cartilage degeneration in the temporomandibular joint (TMJ) of mouse models with osteoarthritis (OA). METHODS: Double-heterozygous (Col11a1- and Ddr2-haploinsufficiency, Col11a1(+/−);Ddr2(+/−)) mice were generated. TMJs of Ddr2(+/−) mice were subjected to partial discectomy. Condylar cartilage from the TMJ of Col11a1(+/−);Ddr2(+/−) mice, surgically treated (discectomy) Ddr2(+/−) mice, and their corresponding controls was characterized by means of histology and evaluated using a scoring system specific to mouse joints...
April 2014: Journal of Oral Pathology & Medicine
Wei Zhao, Cun Zhang, Man Shi, Jian Zhang, Meng Li, Xiaochang Xue, Zhao Zhang, Zhen Shu, Jinyu Zhu, Nan Mu, Weina Li, Qiang Hao, Zhijun Wang, Li Gong, Wei Zhang, Yingqi Zhang
OBJECTIVE: Discoidin domain receptor 2 (DDR-2)/matrix metalloproteinase (MMP) signaling is an important pathway involved in cartilage destruction in rheumatoid arthritis (RA). However, the molecular mechanisms of this pathway have not been clearly identified. This study was undertaken to screen key molecules involved in this pathway and evaluate their biologic functions in synovium invasion of RA. METHODS: DDR-2-interacting proteins were examined in vitro by immunoprecipitation and mass spectrometry, and annexin A2 was acquired...
September 2014: Arthritis & Rheumatology
M L Ricks, J T Farrell, D J Falk, D W Holt, M Rees, J Carr, T Williams, B A Nichols, L C Bridgewater, P R Reynolds, D L Kooyman, R E Seegmiller
OBJECTIVE: Col2a1 gene mutations cause premature degeneration of knee articular cartilage in disproportionate micromelia (Dmm) and spondyloepiphesial dysplasia congenita (sedc) mice. The present study analyses the temporomandibular joint (TMJ) in Col2a1 mutant mice in order to provide an animal model of TMJ osteoarthritis (OA) that may offer better understanding of the progression of this disease in humans. DESIGN: Dmm/+ mice and controls were compared at two, six, nine and 12 months...
September 2013: Archives of Oral Biology
Lia Pulsatelli, Olga Addimanda, Veronica Brusi, Branka Pavloska, Riccardo Meliconi
This review focuses on the new perspectives which can provide insight into the crucial pathways that drive cartilage-bone physiopathology. In particular, we discuss the critical signaling and effector molecules that can activate cellular and molecular processes in both cartilage and bone cells and which may be relevant in cross talk among joint compartments: growth factors (bone morphogenetic proteins and transforming growth factor), hypoxia-related factors, cell-matrix interactions [discoidin domain receptor 2 (DDR2) and syndecan 4], signaling molecules [WNT, Hedgehog (Hh)]...
January 2013: Therapeutic Advances in Chronic Disease
Ikuma Kawai, Tomoka Hisaki, Koji Sugiura, Kunihiko Naito, Kiyoshi Kano
Discoidin domain receptor 2 (DDR2) is a receptor tyrosine kinase that is activated by fibrillar collagens. DDR2 regulates cell proliferation, cell adhesion, migration, and extracellular matrix remodeling. The decrement of endogenous DDR2 represses osteoblastic marker gene expression and osteogenic differentiation in murine preosteoblastic cells, but the functions of DDR2 in chondrogenic cellular proliferation remain unclear. To better understand the role of DDR2 signaling in cellular proliferation in endochondral ossification, we inhibited Ddr2 expression via the inhibitory effect of miRNA on Ddr2 mRNA (miDdr2) and analyzed the cellular proliferation and differentiation in the prechondrocyte ATDC5 cell lines...
October 26, 2012: Biochemical and Biophysical Research Communications
Marijn Rutgers, Daniel B Saris, Lucienne A Vonk, Mattie H van Rijen, Vanessa Akrum, Danielle Langeveld, Antonette van Boxtel, Wouter J Dhert, Laura B Creemers
INTRODUCTION: Current cartilage repair procedures using autologous chondrocytes rely on a variety of carriers for implantation. Collagen types I and II are frequently used and valuable properties of both were shown earlier in vitro, although a preference for either was not demonstrated. Recently, however, fibrillar collagens were shown to promote cartilage degradation. The goal of this study was to evaluate the effects of collagen type I and type II coating on chondrogenic properties of in vitro cultured human chondrocytes, and to investigate if collagen-mediated cartilage degradation occurs...
January 2013: Tissue Engineering. Part A
D W Holt, M L Henderson, C E Stockdale, J T Farrell, D L Kooyman, L C Bridgewater, R E Seegmiller
OBJECTIVE: To test the hypothesis that the spondyloepiphyseal dysplasia congenita (sedc) heterozygous (sedc/+) mouse, a COL2A1 mutant, is a model for the study of osteoarthritis (OA) in the absence of dwarfism and to investigate the presence of HtrA1, Ddr2, and Mmp-13 and their possible involvement in a universal mechanism leading to OA. DESIGN: Whole mount skeletons of adult animals were analyzed to determine whether sedc/+ mice exhibit dwarfism. To characterize progression of osteoarthritic degeneration over time, knee and temporomandibular joints from sedc/+ and wild-type mice were analyzed histologically, and severity of articular cartilage degradation was graded using the Osteoarthritis Research Society International (OARSI) scoring system...
May 2012: Osteoarthritis and Cartilage
Lin Xu, Ilona Polur, Jacqueline M Servais, Sirena Hsieh, Peter L Lee, Mary B Goldring, Yefu Li
Increased expression of the discoidin domain receptor 2 (DDR2) results from its interaction with collagen type II. This induces expression of matrix metalloproteinase (MMP)-13, leading to osteoarthritis (OA). To investigate the impact of the pericellular matrix of chondrocytes on DDR2, we generated a mouse model with inducible overexpression of DDR2 in cartilage. Conditional overexpression of DDR2 in mature mouse articular cartilage was controlled via the cartilage oligomeric matrix protein promoter using the Tet-Off-inducible system...
September 2011: American Journal of Pathology
Lin Xu, Jacqueline Servais, Ilona Polur, Doil Kim, Peter L Lee, Kimberly Chung, Yefu Li
OBJECTIVE: To investigate whether the reduction of discoidin domain receptor 2 (DDR-2), a cell membrane tyrosine kinase receptor for native type II collagen, attenuates the progression of articular cartilage degeneration in mouse models of osteoarthritis (OA). METHODS: Double-heterozygous (type XI collagen-deficient [Col11a1(+/-)] and Ddr2-deficient [Ddr2(+/-)]) mutant mice were generated. Knee joints of Ddr2(+/-) mice were subjected to microsurgical destabilization of the medial meniscus...
September 2010: Arthritis and Rheumatism
Ilona Polur, Peter L Lee, Jacqueline M Servais, Lin Xu, Yefu Li
This study is to investigate the possible role of high temperature requirement A 1 (HtrA1) in the articular cartilage degeneration. Paraffin sections were prepared from the knee and temporomandibular (TM) joints of four mouse OA models; two of the models had a genetic mutation (type IX collagen-deficient and type XI collagen-haploinsufficient) and two were surgically induced (destabilization of the medial meniscus of knee joint and discectomy of TM joint). The HtrA1 protein expression profiles of the prepared sections were examined by immunohistostaining...
May 2010: Histology and Histopathology
Jin Su, Jiangtian Yu, Tingting Ren, Wei Zhang, Yuanqiang Zhang, Xinping Liu, Tiezheng Sun, Houshan Lu, Keiji Miyazawa, Libo Yao
Regulation of matrix metalloproteinase-13 (MMP-13) by collagen matrix in the synovial fibroblasts of rheumatoid arthritis (RA) is critical event in the progressive joint destruction. Our previous study indicated that a collagen receptor, discoidin receptor 2 (DDR2), was highly expressed in the synovial fibroblasts of RA. However, the functional role of DDR2 in the regulation of MMP-13 production in synovial fibroblasts has not been elucidated. In this study, we initially demonstrated that the DDR2 and MMP-13 proteins are both highly expressed in the synovial lining layer of RA...
October 2009: Molecular and Cellular Biochemistry
Andreas R Klatt, Dagmar Zech, Gertrud Kühn, Brigitte Paul-Klausch, Gabriele Klinger, Joerg H Renno, Joachim Schmidt, Gebhart Malchau, Klaus Wielckens
We deciphered constituent parts of a signal transduction cascade that is initiated by collagen II and results in the release of various pro-inflammatory cytokines, including interleukin-6 (IL-6), in primary human chondrocytes. This cascade represents a feed-forward mechanism whereby cartilage matrix degradation is exacerbated by the mutually inducing effect of released collagen II fragments and pro-inflammatory cytokines. We previously proposed discoidin domain receptor 2 as a central mediator in this event...
June 2009: Journal of Pathology
L Xu, I Polur, C Lim, J M Servais, J Dobeck, Y Li, B R Olsen
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...
July 2009: Osteoarthritis and Cartilage
Wei Zhang, Tianbing Ding, Jian Zhang, Jin Su, Jiangtian Yu, Jipeng Li, Fuyang Li, Chunmei Wang, Nannan Liu, Xinping Liu, Wenyu Ma, Libo Yao
Discoidin domain receptor 2 (DDR2) is a kind of protein tyrosine kinases associated with cell proliferation and tumor metastasis, and collagen, a ligand for DDR2, up-regulates matrix metalloproteinase 1 (MMP-1) and MMP-2 expression in extracellular matrix (ECM). To investigate the role of DDR2 in cartilage destruction in rheumatoid arthritis (RA), we expressed the extracellular domain (ECD) of DDR2 (without signal peptide and transmembrane domain, designated DR) in insect cells, purified and characterized DR, hoping to use it as a specific antagonist of DDR2...
September 1, 2007: Journal of Cellular Biochemistry
N P Lam, Y Li, A B Waldman, J Brussiau, P L Lee, B R Olsen, L Xu
Our previous studies demonstrated that mutations in type IX and type XI collagens in mice caused osteoarthritis (OA)-like changes in knee and temporomandibular (TM) joints. We also found that the overexpression of matrix metalloproteinase 13 (Mmp-13) was probably due to the up-regulation of a collagen receptor, discoidin domain receptor 2 (Ddr2), which was responsible for knee cartilage degeneration in mutant mice. The objective of our study was to determine whether the expression of Mmp-3, Mmp-13 and Ddr2 was increased in OA-like TM joints in mutant mice using immunohistochemistry...
June 2007: Archives of Oral Biology
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