bone; and osteoclasts,which resorb bone by acidification. Osteoclastic
activity uses protons(H+) derived from carbonic acid formed by the
enzymecarbonic anyhydrase.Carbonic anhydrases are zinc-containing
enzymes that catalyse the reversible reaction between carbon dioxide
hydration and bicarbonate dehydration:
H 2 O+CO 2 ↔H++HCO 3 −
In the region of the ruffled border, protons and lysosomal enzymes,
such as acid phosphatase, are released into a sealed zone (Howship’s
lacuna). Breakdown of bone occurs due to the acidification of this extra-
cellular compartmentthat is analogous to an intracellular secondary lyso-
some. Bone deposition is regulated primarily by parathyroid hormone
(PTH),which is secreted in response to low serum calcium levels. PTH
increases serum calcium as summarized below. The increased serum cal-
cium inhibits PTH secretion by negative feedback. PTH stimulates:
- osteoclaststo resorb bone (through PTH receptors on osteoblasts),
- renal synthesis of 1,25-dihydroxycholecalciferol, which in turn
increases intestinal absorption of Ca++. - intestinal absorption of Ca++.
20 Anatomy, Histology, and Cell Biology
PTH1,25 (OH) 2D
(renal synthesis)Ca++ Gut
AbsorptionBone Resorption
Osteoclasts
Ruffled BordersPTH regulates osteoclasts by an indirect mechanism throughPTH
receptors on osteoblasts. There arenoPTH receptors on osteoclasts. PTH
stimulation of osteoblasts releasesmacrophage colony-stimulating factor
(M-CSF)andRANK-L.M-CSF stimulates differentiation ofmonocytes
into osteoclasts. RANK-L is found in both membrane and soluble forms
and binds toRANK (receptor for activation of nuclear factor kappa B)
on osteoclasts and osteoclast precursors stimulating osteoclastic activation/
ruffled border formation.Osteoprotegerin (OPG) is a decoy receptor for