Disturbed Synthesis of Type II Collagen Interferes with Rate of Bone Formation and Growth and Increases Bone Resorption in Transgenic Mice (original) (raw)
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Journal of Anatomy, 1997
Skull morphology and histology in the heterozygous offspring of a transgenic founder mouse Del1, harbouring 6 copies of deletion mutation in Col2a1 gene, were compared with those in normal siblings. On visual observation and roentgenocephalometric examination the heads of heterozygous Del1 mice were smaller than normal. Histologically the sizes of cartilaginous structures of the cranial base were reduced. Severe defects were seen in the temporomandibular joint as progressive osteoarthritic lesions. These observations elucidate the relationship between the genotype and phenotype and demonstrate that heterozygous Del1 mice are a useful model for studies on a genetic disturbance where ' clinical ' manifestations are not evident until adult age.
Osteoarthritis and Cartilage, 2000
Objective: The present study was conducted on transgenic Del1 (+/−) mice harboring six copies of a transgene with small deletion mutation engineered into mouse type II collagen gene. Incorporation of transgene into mouse genome was predicted to cause reduced mechanical strength of articular cartilage with deposition of structurally inferior collagen network and consequently to predispose the animal to early-onset joint degeneration.
Bone growth retardation in mouse embryos expressing human collagenase 1
AJP: Cell Physiology, 2007
Cellular growth and differentiation are readouts of multiple signaling pathways from the intercellular and/or extracellular milieu. The extracellular matrix through the activation of cellular receptors transmits these signals. Therefore, extracellular matrix proteolysis could affect cell fate in a variety of biological events. However, the biological consequence of inadequate extracellular matrix degradation in vivo is not clear. We developed a mouse model expressing human collagenase (matrix metalloproteinase-1, MMP-1) under the control of Col2a1 promoter. The mice showed significant growth retardation during embryogenesis and a loss of the demarcation of zonal structure and columnar array of the cartilage. Immunological examination revealed increased degradation of type II collagen and upregulation of fibronectin and α5-integrin subunit in the transgenic cartilage. The resting zone and proliferating zone of the growth plate cartilage exhibited a simultaneous increase in bromodeoxy...
Tissue-specific expression of the human type II collagen gene in mice
Proceedings of the National Academy of Sciences, 1987
Type II collagen is crucial to the development of form in vertebrates as it is the major protein of cartilage. To study the factors regulating its expression we introduced a cosmid containing the human type II collagen gene, including 4.5 kilobases of 5' and 2.2 kilobases of 3' flanking DNA, into embryonic stem cells in vitro. The transformed cells contribute to all tissues in chimeric mice allowing the expression of the exogenous gene to be studied in vivo. Human type II collagen mRNA is restricted to tissues showing transcription from the endogenous gene and human type II collagen is found in extracellular matrix surrounding chondrocytes in cartilage. The results indicate that the cis-acting requirements for correct temporal and spatial regulation of the gene are contained within the introduced DNA.
Developmental Dynamics, 2011
We report the generation of a new mouse strain harboring a Col2-pd2EGFP reporter transgene; pd2EGFP has a much shorter half-life than EGFP, making it a near real-time reporter for Col2a1 expression in vivo and in vitro. In the post-natal growth plate, pd2EGFP fluorescence was expressed in almost all proliferative chondrocytes and in some hypertrophic chondrocytes based on localization with type X collagen. In articular cartilage, pd2EGFP fluorescence diminished over time, nicely illustrating the decrease of type II collagen synthesis in articular chondrocytes during growth. Monolayers of FACS-sorted chondrocytes from P1-2 mice showed faster loss of pd2EGFP compared to EGFP, reflecting rapid chondrocyte de-differentiation. High-density culture of FACS-pd2EGFP-growth plate chondrocytes revealed the typical temporal expression pattern in which type II collagen preceded type X collagen matrix deposition. The Col2-pd2EGFP reporter mouse will be a valuable tool for studies of growth plate chondrocyte biology.
The effect of type II collagen on MSC osteogenic differentiation and bone defect repair
Biomaterials, 2014
The function of type II collagen in cartilage is well documented and its importance for long bone development has been implicated. However, the involvement of type II collagen in bone marrow derived mesenchymal stem cell (BMSC) osteogenesis has not been well investigated. This study elucidated the pivotal role of type II collagen in BMSC osteogenesis and its potential application to bone healing. Type II collagen-coated surface was found to accelerate calcium deposition, and the interaction of osteogenic medium-induced BMSCs with type II collagen-coated surface was mainly mediated through integrin a2b1. Exogenous type II collagen directly activated FAK-JNK signaling and resulted in the phosphorylation of RUNX2. In a segmental defect model in rats, type II collagen-HA/TCP-implanted rats showed significant callus formation at the reunion site, and a higher SFI (sciatic function index) scoring as comparing to other groups were also observed at 7, 14, and 21 day post-surgery. Collectively, type II collagen serves as a better modulator during early osteogenic differentiation of BMSCs by facilitating RUNX2 activation through integrin a2b1-FAK-JNK signaling axis, and enhance bone defect repair through an endochondral ossification-like process. These results advance our understanding about the cartilaginous ECM-BMSC interaction, and provide perspective for bone defect repair strategies.
The effects of type VI collagen on the bone formation
2016
Type VI collagen(Col VI)is a component of the extracellular matrix(ECM)in the periosteum and thought to regulate osteoblast behaviors. Several in vitro studies indicate that osteoblast-lineage cells required attachment to Col VI at early stages of differentiation. In addition, Col6a1-deficient mice displayed a reduction in bone mineral density and cancellous bone mass, and an aberrance of the collagen arrangement of the cortical bone. Therefore, Col VI is suggested to play an important role in normal bone formation during fetal and postnatal development. In several cell types, Col VI interacts with Neural/Glial Antigen 2(NG2)on the cytoplasmic membrane to promote cell proliferation, spreading, and motility. However, the detailed functions of Col VI on the bone formation are still remained unclear. The aim of this entire study is to clarify the functions of Col VI on behaviors of the osteoblast lineages and the bone formation. First of all, I propose to elucidate the spatiotemporal r...
Bone, 1988
Collagen turnover during rat long bone development and growth was investigated using immunofluorescence methods with specific polyclonal antibodies against native (triple helix) and denatured (breakdown products) forms of type I and II collagen. Labeling of cryostat sections with anti-native and denatured collagen type II antibodies resulted in a positive staining throughout the cartilage matrix of fetal and adult long bones. Likewise, native and denatured type I collagen could be detected in mineralized and non-mineralized bone matrix. Moreover, labeling with anti-denatured type I antibody evoked a strong intracellular staining of osteoblasts, but not of osteocytes. Denatured type I was also Irralized intra-pericellularly in the small chondrocytes comprising the primitive cartilage cores and the epiphyses of older long bones. On the other hand, apart from its localization in the cartilage matrix, denatured type II collagen was found specifically within the chondrocytes. These observations indicate that a continuous turnover of the major collagen types takes place in fetal and adult rat long bone tissue. Degradation of collagen apparently occurs intra-and extracellularly, and is mainly independent of the presence and activity of osteoclasts. The presence of denatured type I collagen in cartilage suggests that chondrocytes synthesize small amounts of type I collagen, which is immediately degraded to a denatured form .
Developmental Dynamics, 1994
We have examined the biological and biomechanical consequences of defective type I1 collagen production for fracture repair employing a genetically engineered mouse line Dell which was generated by microinjection of a 39-kb mouse procul(I1) collagen gene construct containing a deletion of exon 7 and intron 7 (Metsaranta et al. [19921 J. Cell Biol. 118203-212). Standardized tibia1 fractures were produced in transgenic Dell mice and their nontransgenic littermates were used as controls. The fracture callus tissues were analyzed at days 7, 9, 14, 28, and 42 using radiography, 0 1994 WILEY-LISS, INC.