DDR2 cartilage

The tyrosine kinase family receptor of discoidin domain receptors (DDR1 and DDR2) is known to be activated by extracellular matrix collagen catalytic binding protein receptors. They play a remarkable role in cell proliferation, differentiation, migration, and cell survival. DDR1 of the DDR family regulates matrix-metalloproteinase, which causes extracellular matrix (ECM) remodeling and reconstruction during unbalanced homeostasis. Collagenous-rich DDR1 triggers the ECM of cartilage to regenerate the cartilage tissue in osteoarthritis (OA) and temporomandibular disorder (TMD)...

Development of the craniofacial skeleton requires interactions between progenitor cells and the collagen-rich extracellular matrix (ECM). The mediators of these interactions are not well-defined. Mutations in the discoidin domain receptor 2 gene ( DDR2 ), which encodes a non-integrin collagen receptor, are associated with human craniofacial abnormalities, such as midface hypoplasia and open fontanels. However, the exact role of this gene in craniofacial morphogenesis is not known. As will be shown, Ddr2 -deficient mice exhibit defects in craniofacial bones including impaired calvarial growth and frontal suture formation, cranial base hypoplasia due to aberrant chondrogenesis and delayed ossification at growth plate synchondroses...

The aim of the study was to correlate the immunohistochemical expression of cartilage intermediate layer protein 2 (CILP-2) and discoidin domain receptor 2 (DDR2), and the ultrastructural changes in the cartilage with the degree of articular cartilage damage in osteoarthritis (OA) patients. Cartilage samples were obtained from twenty patients aged from 46 to 68 years undergoing total knee arthroplasty. In each patient, medial and lateral tibial plateau samples were analysed applying OARSI histopathology grading...

Discoidin Domain Receptor 2 (DDR2) is a collagen-activated receptor kinase that, together with integrins, is required for cells to respond to the extracellular matrix. Ddr2 loss-of-function mutations in humans and mice cause severe defects in skeletal growth and development. However, the cellular functions of Ddr2 in bone are not understood. Expression and lineage analysis showed selective expression of Ddr2 at early stages of bone formation in the resting zone and proliferating chondrocytes and periosteum...

BACKGROUND: Discoidin domain receptor 2 ( Ddr2 ) is a rate-limiting factor in articular cartilage degeneration, a condition which normally leads to joint destruction. In human osteoarthritic tissues and mouse models of osteoarthritis (OA), the expression of Ddr2 increases and interacts with collagen type II, inducing the expression of matrix metalloproteinase 13 (MMP-13) and the receptor itself in chondrocytes. Moreover, conditional deletion of Ddr2 can significantly delay the progression of articular cartilage degeneration in post-traumatic OA mouse models...

Discoidin domain receptor2 (DDR2), a cell membrane tyrosine kinase on chondrocytes surface plays main role in cell-ECM interaction during the progressive degeneration of articular cartilage in osteoarthritis. The degraded component of ECM, type II collagen upon DDR2 binding provokes synthesis of matrix metalloproteinases (MMPs), responsible for severe destruction of joint tissues. DDR2 knockout has been investigated to decline the expression of MMP-1 and 13. Previously, various molecules were effective in preclinical level against different targets in OA, but found to be collapsed in clinical trial due to insufficient target specificity and clinical toxicity...

BACKGROUND: The mutant chondrodysplasia (cho) is a cartilage-targeting disorder in C57BL mice that results in dwarfing and other malformations stemming from this collagenopathy. Clarke Fraser made the discovery of the mutation accidentally in the early 1960s during the thalidomide tragedy. METHODS: For this review we identified key research on cho as since its discovery. Relevant data were compiled to make a comprehensive review that details discoveries associated with the cho mutation, that describes the associated phenotypes and molecular mechanisms, and that provides a discussion surrounding its current clinical relevance...

Spondylo-meta-epiphyseal dysplasia, short limb-abnormal calcification type, is a rare autosomal recessive disorder of the skeleton characterized by disproportionate short stature with narrow chest and dysmorphic facial features. The skeletal manifestations include platyspondyly, short flared ribs, short tubular bones with abnormal metaphyses and epiphyses, severe brachydactyly, and premature stippled calcifications in the cartilage. The abnormal calcifications are so distinctive as to point to the definitive diagnosis...

Temporomandibular joint (TMJ) disorders are often associated with development of osteoarthritis-like changes in the mandibular condyle. Discoidin domain receptor 2 (DDR2), a collagen receptor preferentially activated by type I and III collagen found in the TMJ and other fibrocartilages, has been associated with TMJ degeneration, but its role in normal joint development has not been previously examined. Using Ddr2 LacZ-tagged mice and immunohistochemistry, we found that DDR2 is preferentially expressed and activated in the articular zone of TMJs but not knee joints...

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...

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...

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...

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)...

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...

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...

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...

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...

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)]...

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...

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...