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PTH effects on bone. PTH binds to osteoblast parathyroid hormone receptor 1 (PTHR1), stimulating the cell surface expression of RANKL, which binds to
RANK, a cell surface protein on osteoclast precursors. Binding of RANKL to RANK activates osteoclast gene transcription and the differentiation into a
mature osteoclast, characterized by the ruffled membrane under which bone resorption occurs. Osteoclasts attach to the bone surface through β-integrins
generating an isolated extracellular microenvironment. Acidic intracellular vesicles fuse to the cell membrane facing the bone matrix forming the scalloped
or ruffled border. Hydrogen ions generated by carbonic anhydrase II are delivered across the plasma membrane by H+-ATPases recruited into the cell’s
ruffled membrane. The acidification of this isolated extracellular
microenvironment to a pH of approximately 4 favors the dissolving of hydroxyapatite and
Source: Chapter 5. Parathyroid Gland and Ca2+ and PO - Regulation, Endocrine Physiology, 4e
provides optimal conditions for the action of the lysosomal proteases4including collagenase and cathepsins to dissolve bone mineral. The products of bone
Molina PE.
Physiology,
4e; 2013 Available
at: http://mhmedical.com/
Accessed:surface
August providing
09, 2017 ionized Ca++, inorganic
degradation Citation:
are endocytosed
byEndocrine
the osteoclast
and transported
to and released
at the cell’s antiresorptive
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phosphate, and alkaline phosphatases, into circulation. Osteoprotegerin, secreted by osteoblasts serves as a decoy ligand for RANKL, preventing binding
of RANKL to RANK, thereby inhibiting the process of osteoclastic bone resorption. Production of osteoprotegerin is increased by estrogen and decreased
by glucocorticoids and PTH. ATPase, adenosine triphosphatase; PTH, parathyroid hormone; RANK, receptor activator of nuclear factor-κB; RANKL,