Osteoprotegerin-Receptor Activator of Nuclear Factor-[kappa]B
Osteoprotegerin-Receptor Activator of Nuclear Factor-[kappa]B
Osteoporosis, the most commonly occurring bone disease, is characterized by enhanced bone fragility and increased risk of fracture. Bone remodeling is the process in which bone is broken down by osteoclasts and then built back again by osteoblasts. In healthy adult bone, these two processes are balanced and a constant level of bone mass is maintained. Some of the proteins involved in the interaction between osteoblasts and osteoclasts have recently been identified. Receptor activator of nuclear factor-κB (RANK) ligand is produced by osteoblasts and exerts its effects through binding to its receptor (RANK) on osteoclast precursor cells. Binding results in activation of osteoclasts. Osteoblasts also produce osteoprotegerin (OPG), a potent inhibitor of osteoclast formation and a decoy receptor for RANK. The relative ratio of OPG and RANK ligand in the bone marrow microenvironment may determine the number of active osteoclasts, bone resorption rate, and bone mass. OPG is currently under investigation for osteoporosis treatment.
Osteoporosis, the most commonly occurring bone disease, is characterized by low bone mass together with microarchitectural deterioration. This leads to a consequent increase in bone fragility and susceptibility to fractures. Bones most likely to break are in the wrist, spine, and hip. Osteoporosis is the leading cause of serious morbidity and functional loss in the elderly. The prevalence of low bone mass increases with increasing age in both men and women. It is higher for women than men because accelerated bone loss is associated with estrogen decline in the immediate postmenopausal period. In the United States, approximately 1.5 million osteoporotic fractures occur per year. One in two women and one in eight men over 50 will have an osteoporotic fracture.
The mature skeleton is a metabolically active organ that undergoes continuous remodeling by a process that replaces old bone with new bone. Remodeling is necessary to maintain the structural integrity of the skeleton and to serve its metabolic functions as a storehouse of calcium and phosphorus. This dual function often comes into conflict under conditions of changing mechanical forces or of nutritional and metabolic stress. Cells responsible for bone formation, the osteoblasts originate from precursor cells that then differentiate into mature osteoblasts. Osteoblast precursors originate from bone marrow stromal cells. Osteoclasts responsible for bone resorption originate from hematopoietic stem cells known as monocytes.
The remodeling cycle is finely regulated by a variety of systemic and local factors, for example, estrogen (E2), parathyroid hormone (PTH), vitamin D, growth factors, and cytokines. Bone formation and resorption are usually balanced and a constant level of bone mass is maintained. An imbalance between bone formation and resorption causes metabolic diseases such as osteoporosis and osteopetrosis (a family of diseases characterized by increased bone mass due to decreased bone resorption).
Osteoporosis, the most commonly occurring bone disease, is characterized by enhanced bone fragility and increased risk of fracture. Bone remodeling is the process in which bone is broken down by osteoclasts and then built back again by osteoblasts. In healthy adult bone, these two processes are balanced and a constant level of bone mass is maintained. Some of the proteins involved in the interaction between osteoblasts and osteoclasts have recently been identified. Receptor activator of nuclear factor-κB (RANK) ligand is produced by osteoblasts and exerts its effects through binding to its receptor (RANK) on osteoclast precursor cells. Binding results in activation of osteoclasts. Osteoblasts also produce osteoprotegerin (OPG), a potent inhibitor of osteoclast formation and a decoy receptor for RANK. The relative ratio of OPG and RANK ligand in the bone marrow microenvironment may determine the number of active osteoclasts, bone resorption rate, and bone mass. OPG is currently under investigation for osteoporosis treatment.
Osteoporosis, the most commonly occurring bone disease, is characterized by low bone mass together with microarchitectural deterioration. This leads to a consequent increase in bone fragility and susceptibility to fractures. Bones most likely to break are in the wrist, spine, and hip. Osteoporosis is the leading cause of serious morbidity and functional loss in the elderly. The prevalence of low bone mass increases with increasing age in both men and women. It is higher for women than men because accelerated bone loss is associated with estrogen decline in the immediate postmenopausal period. In the United States, approximately 1.5 million osteoporotic fractures occur per year. One in two women and one in eight men over 50 will have an osteoporotic fracture.
The mature skeleton is a metabolically active organ that undergoes continuous remodeling by a process that replaces old bone with new bone. Remodeling is necessary to maintain the structural integrity of the skeleton and to serve its metabolic functions as a storehouse of calcium and phosphorus. This dual function often comes into conflict under conditions of changing mechanical forces or of nutritional and metabolic stress. Cells responsible for bone formation, the osteoblasts originate from precursor cells that then differentiate into mature osteoblasts. Osteoblast precursors originate from bone marrow stromal cells. Osteoclasts responsible for bone resorption originate from hematopoietic stem cells known as monocytes.
The remodeling cycle is finely regulated by a variety of systemic and local factors, for example, estrogen (E2), parathyroid hormone (PTH), vitamin D, growth factors, and cytokines. Bone formation and resorption are usually balanced and a constant level of bone mass is maintained. An imbalance between bone formation and resorption causes metabolic diseases such as osteoporosis and osteopetrosis (a family of diseases characterized by increased bone mass due to decreased bone resorption).
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