Browsing by Subject "Growth plate"

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    Genetic mouse models for the functional analysis of the perifibrillar components collagen IX, COMP and matrilin-3: Implications for growth cartilage differentiation and endochondral ossification
    (Murcia : F. Hernández, 2009) Zaucke, Frank; Grässel, Susanne
    The mutual interaction of the two supramolecular compartments, the fibrillar and extrafibrillar matrix is a prerequisite for stability and integrity of the cartilage extracellular matrix. The fibrillar periphery, composed of collagen IX, matrilins and cartilage oligomeric matrix protein (COMP) among other components, constitutes the interface which mediates interactions between the two compartments. Mutations in these peripheral macromolecules cause a broad spectrum of skeletal conditions such as pseudoachondroplasia (PSACH) and multiple epiphyseal dysplasia (MED), which severely affect the organization and integrity of the cartilage growth matrix in humans. Transgenic and knockout mouse models for collagen IX, matrilin-3 and COMP and combinations thereof display cartilage abnormalities and pathologies of varying severity. Absence of collagen IX appears to cause the most severe growth plate phenotype with a profoundly disturbed morphological organization affecting size and shape of the long bones. Notably, similar growth plate phenotypes, including irregularities in the proteoglycan content, hypocellular central regions, disorganized proliferation columns with atypically shaped and oriented chondrocytes and alterations in the hypertrophic zone are observed in transgenic mice lacking other macromolecules or carrying mutations therein. These include collagens II and XI, integrin subunits, integrin linked kinase (ILK), HIF-1α, VEGFα and the tumor suppressor PTEN. Notably, mutations in ciliar proteins such as Kif3α, polaris or Smo/Gli severely affect the ability of chondrocytes to move and to become arranged in columns. Absence or mutational changes of a variety of different, non-related cartilage macromolecules apparently cause similar pathologies and abnormalities of the growth cartilage, suggesting a limited number of underlying molecular mechanisms
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    The hypertrophic chondrocyte: To be or not to be
    (Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2021) Hallett, Shawn A.; Ono, Wanida; Ono, Noriaki
    Hypertrophic chondrocytes are the master regulators of endochondral ossification; however, their ultimate cell fates cells remain largely elusive due to their transient nature. Historically, hypertrophic chondrocytes have been considered as the terminal state of growth plate chondrocytes, which are destined to meet their inevitable demise at the primary spongiosa. Chondrocyte hypertrophy is accompanied by increased organelle synthesis and rapid intracellular water uptake, which serve as the major drivers of longitudinal bone growth. This process is delicately regulated by major signaling pathways and their target genes, including growth hormone (GH), insulin growth factor-1 (IGF-1), indian hedgehog (Ihh), parathyroid hormone-related protein (PTHrP), bone morphogenetic proteins (BMPs), sex determining region Y-box 9 (Sox9), runt-related transcription factors (Runx) and fibroblast growth factor receptors (FGFRs). Hypertrophic chondrocytes orchestrate endochondral ossification by regulating osteogenic-angiogenic and osteogenic-osteoclastic coupling through the production of vascular endothelial growth factor (VEGF), receptor activator of nuclear factor kappa-B ligand (RANKL) and matrix metallopeptidases-9/13 (MMP-9/13). Hypertrophic chondrocytes also indirectly regulate resorption of the cartilaginous extracellular matrix, by controlling formation of a special subtype of osteoclasts termed "chondroclasts". Notably, hypertrophic chondrocytes may possess innate potential for plasticity, reentering the cell cycle and differentiating into osteoblasts and other types of mesenchymal cells in the marrow space. We may be able to harness this unique plasticity for therapeutic purposes, for a variety of skeletal abnormalities and injuries. In this review, we discuss the morphological and molecular properties of hypertrophic chondrocytes, which carry out important functions during skeletal growth and regeneration.