Osteoclast
A large, multinucleated bone-resorbing cell derived from the monocyte–macrophage lineage. It dissolves mineral with acid and digests collagen with proteases in a sealed resorption compartment.
Overview
Osteoclasts form by fusion of haematopoietic monocyte–macrophage precursors (not mesenchymal cells) under the influence of M-CSF and RANKL; they typically have 5–50 nuclei and are 50–100 µm across. An active osteoclast attaches to bone via αvβ3 integrin forming a ring-like sealing zone (actin ring) that isolates a resorption compartment beneath a deeply folded ruffled border.
Into this compartment it pumps H⁺ via a vacuolar H⁺-ATPase (protons generated by carbonic anhydrase II, with Cl⁻ following via ClC-7), lowering the pH to ≈4.5 and dissolving hydroxyapatite; then cathepsin K and matrix metalloproteinases digest the exposed collagen. The excavated pit is a Howship lacuna (resorption bay); degradation products are endocytosed and released at the basolateral surface (transcytosis). Osteoclasts are rich in tartrate-resistant acid phosphatase (TRAP), a histochemical marker.
Calcitonin receptors on osteoclasts cause rapid retraction and inactivation; oestrogen promotes osteoclast apoptosis. Osteoclasts lack PTH receptors — PTH acts on them indirectly via osteoblast RANKL.
- Location
Bone surfaces undergoing resorption — Howship lacunae on trabeculae, cutting cones in cortical bone, growth-plate metaphysis.
Anatomy
- Histology
Large acidophilic multinucleated cells lying in shallow pits (Howship lacunae); ruffled border, clear zone and abundant lysosomes and mitochondria on electron microscopy.
Function
- Resorb bone matrix and mineral
- Release calcium and phosphate into the blood
- Shape bones during growth (modelling) and clear damaged bone (remodelling)
- Hollow out the medullary cavity
- Regulation
Stimulated by RANKL, M-CSF, PTH (indirect), calcitriol (indirect), IL-1, IL-6, TNF-α; inhibited by OPG, calcitonin, oestrogen, bisphosphonates and denosumab.
Clinical significance
Bisphosphonates and denosumab
Bisphosphonates (pyrophosphate analogues) bind hydroxyapatite and are taken up by osteoclasts, inhibiting farnesyl pyrophosphate synthase → apoptosis. Denosumab is an anti-RANKL antibody. Both reduce fractures; rare adverse effects include osteonecrosis of the jaw and atypical femoral fractures.
Osteopetrosis
Defective osteoclast acidification (e.g. carbonic anhydrase II, TCIRG1 or CLCN7 mutations) → dense, brittle "marble" bones, marrow failure with extramedullary haematopoiesis and cranial nerve palsies.
Mnemonics
Blasts vs clasts
OsteoBlasts Build bone; osteoClasts Chew (or Cut) bone.
Test yourself
Parathyroid hormone increases osteoclastic bone resorption mainly by which mechanism?
- Binding directly to PTH receptors on mature osteoclasts
- Increasing osteoprotegerin secretion
- Inhibiting calcitriol synthesis
- Increasing RANKL expression by osteoblasts
Answer: Increasing RANKL expression by osteoblasts
Osteoclasts lack PTH receptors. PTH acts on osteoblasts (and osteocytes), raising RANKL and lowering OPG; RANKL binds RANK on osteoclast precursors, promoting their differentiation and activity. PTH also stimulates renal 1α-hydroxylase, increasing calcitriol.
Compiled from standard anatomy and physiology references — see the Skeletal System sources. For education only; not medical advice.