How are autophagic processes involved in bone mineralisation?
Bone formation is made up of two different processes: first, osteoblasts produce collagen-containing osteoid, and then mineral crystals (hydroxyapatite) accumulate within the osteoid to make the hard mineralized bone substance. The mechanisms that control the balance between these two processes are not known, but if they are defective, it leads to brittle bones that break easily. Some examples of this are osteogenesis imperfecta, and osteoporosis. Understanding how these processes are controlled could lead to new ways to strengthen weak bones.
Our recent discoveries indicate that intracellular vesicles, including autophagy (intracellular recycling), are involved in mineral secretion by osteoblasts and osteocytes. We have carried out RNA-sequencing in bones from mice with brittle bones, and found changes in a range of autophagic genes. This provides new information about the way that cells in the skeleton control bone composition.
This project will use cell culture techniques, gene knockdown studies, and cell-based assays such as confocal immunofluorescence, molecular biology, reporter assays, and quantitative PCR techniques to determine the function of these autophagic genes in osteocytes and osteoblasts.
Prof Natalie Sims
Bone cell biology & disease
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