Osteoclast differentiation parathyroid hormone

Three hormones serve as the principal regulators of calcium and phosphate homeostasis parathyroid hormone (PTH), fibroblast growth factor 23 (FGF23), and the steroid vitamin D (Figure 42-2). Vitamin D is a prohormone rather than a true hormone, because it must be further metabolized to gain biologic activity. PTH stimulates the production of the active metabolite of vitamin D, l,25(OH)2D. l,25(OH)2D, on the other hand, suppresses the production of PTH. l,25(OH)2D stimulates the intestinal absorption of calcium and phosphate. l,25(OH)2D and PTH promote both bone formation and resorption in part by stimulating the proliferation and differentiation of osteoblasts and osteoclasts. Both... 

Bone is a relatively dynamic organ that undergoes significant turnover that is, hone resorption and deposition it is broken down hy osteoclasts and rebuilt by osteoblasts. Besides an adequate supply of calcium, a close cooperation is required between these two types of cell. Complex signalling pathways achieve proper rates of growth and differentiation these pathways include the action of several hormones, including parathyroid hormone (PTH), vitamin D, growth hormone, steroids and calcitonin, as well as several cytokines. 

Bones are constantly dissolved by osteoclasts and remineralized by osteoblasts in response to mechanical forces. Osteoclasts possess an acidic compartment and pass demineralized bone products to the periosteum (Sect. 1). They develop in stress-induced bony microcracks and are activated by differentiation factors secreted by osteoblasts, especially after menopause. Menopausal osteoporosis is controlled by drugs that are a stable form of pyrophosphate (bisphosphonate) or cathepsin K inhibitors (Sect. 2). The calcium ion concentration of blood is raised by parathyroid hormone and a vitamin D derivative called calcitriol. Parathyroid hormone causes kidneys to excrete phosphate, retain calcium, and activate calcitriol production (Sect. 3). Calcitriol induces calcium transporter proteins in osteoclasts and intestinal epithelium, where they move calcium from bone or diet into blood (Sect. 4). The chapter concludes with a discussion of calcitonin which lowers blood calcium concentrations by reversing parathyroid hormone effects on the kidney and inhibiting osteoclast activity (Sect. 5). 

Injury, infection, stress-induced hormones (glucocorticoids), parathyroid hormone (Sect. 10.3.1), and increased pressure on a bone all decrease osteoprotegerin (OCIF) production by osteoblasts, causing greater differentiation of osteoclasts, more bone remodeling, and more... 

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