Understanding the osteoimmunological role of roquin in the maintenance of bone homeostasis

Bay Lim

    Research output: ThesisDoctoral Thesis

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    Abstract

    [Truncated] The bone organ system is a dynamic mineralized tissue that is continuously being broken down and rebuilt in a process known as bone remodelling. The remodelling process is an important metabolic activity involved in the maintenance of the homeostasis and architecture of bone while performing its versatile functions. The bone remodelling process is a coupled activity between the catabolic effects of boneresorbing osteoclasts and the anabolic effects of bone-forming osteoblasts.

    The remodelling cycle begins when there is an external mechanical stimulus, which initiates accessory cells including osteoblasts to secrete RANKL. RANKL binds onto the cell surface receptor RANK displayed on osteoclast precursors that originate from the haematopoietic stem cells. The RANKL-RANK interaction drives osteoclastogenesis and cell fusion to form large multinucleated osteoclasts. Once mature, osteoclasts begin to secrete proteolytic enzymes to resorb the bone matrix. The bone erosion by osteoclasts is a crucial process in remoulding the bone tissue.

    To prevent osteoclasts from continuously resorbing bone, osteoblasts, which are derived from mesenchymal stem cells, also secrete regulatory molecules such as OPG. OPG acts as a decoy receptor that binds onto RANKL to prevent RANKL-RANK interaction. Such interactions allow osteoblasts to modulate the bone remodelling cycle, balancing bone resorption and bone formation. Mature osteoblasts are the primary matrixproducing cells that build and mineralise bone. As a result, some become entombed within their own matrix and differentiate into osteocytic cells with long dendritic processes to maintain cell-cell contact amongst themselves and with bone cells residing on the surfaces of bone. Osteocytes are generally recognised as the mechanotransducers of bone tissue, responding to mechanical stimuli and generating signals that play important roles in regulating the bone remodelling cycle.

    Original languageEnglish
    QualificationDoctor of Philosophy
    Publication statusUnpublished - 2014

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