Bone Aging, Cellular Senescence, and Osteoporosis

A s part of the skeleton, bone tissue functions to support locomotion, hematopoiesis, glucose metabolism, interactions with the renal and reproductive systems, and reservoirs for phosphorus and calcium, as well as protection for internal organs. Bone is made up of extracellular matrix proteins, inorganic mineral in the form of hydroxyapatite, and many resident cell types

Robert J Pignolo

2021

Scholarcy highlights

  • A s part of the skeleton, bone tissue functions to support locomotion, hematopoiesis, glucose metabolism, interactions with the renal and reproductive systems, and reservoirs for phosphorus and calcium, as well as protection for internal organs. Bone is made up of extracellular matrix proteins, inorganic mineral in the form of hydroxyapatite, and many resident cell types
  • The formation of bone during normal development and accrual after physiological growth plate closure mainly occurs in the first two decades of life in healthy individuals, after which BMD plateaus and is followed by age-related bone loss. Osteoporosis in women typically occurs during the postmenopausal period, and in both women and men caused by age-related changes
  • Osteoclast differentiation is promoted by osteoblasts, osteocytes, and activated T lymphocytes by the secretion of receptor activator of nuclear factor kappa-B ligand, which binds to the RANK receptor on the osteoclast surface. RANK receptor expression is increased by the binding of macrophage colony-stimulating factor, secreted by osteoblasts and bone marrow stromal cells,(10) to the colonystimulating factor-1 receptor known as c-FMS on the osteoclast surface
  • Osteoclast differentiation and activity can be inhibited by osteoprotegerin, a decoy receptor that binds RANKL and is secreted by osteoblasts, osteocytes, B lymphocytes, and the liver
  • There is growing evidence to suggest that cellular senescence in bone can be triggered by reactive oxygen species, DNA damage, telomere dysfunction, and heterochromatin changes, depending on the cell type. miRNAs serve to modulate critical switching points, such as those between osteogenesis and adipogenesis, and aspects of the senescence program
  • Senolytic compounds are currently being evaluated in interventional clinical trials

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