Musculoskeletal, Skin & Connective Tissue

The osteoblast forms bone by secreting osteoid (type I collagen + matrix), which it then mineralizes. Osteoblasts derive from mesenchymal stem cells.

The osteoclast is a large multinucleated cell from the monocyte/macrophage (hematopoietic) lineage that resorbs bone by secreting H+ and acid hydrolases, dissolving hydroxyapatite and collagen.

Osteoblasts express RANKL, which binds RANK on osteoclast precursors to stimulate their differentiation and activity. Osteoblasts also secrete osteoprotegerin (OPG), a decoy receptor that binds RANKL and inhibits osteoclastogenesis.

Endochondral ossification replaces a cartilage model with bone (forms long bones and the axial skeleton). Intramembranous ossification forms bone directly from mesenchyme without a cartilage intermediate (forms flat bones of the skull, clavicle).

Hydroxyapatite, a crystalline calcium phosphate [Ca10(PO4)6(OH)2], deposited on a scaffold of type I collagen.

PTH (1) stimulates osteoclastic bone resorption (indirectly via RANKL), (2) increases renal Ca2+ reabsorption in the distal tubule while promoting phosphate excretion, and (3) stimulates renal 1-alpha-hydroxylase to produce active vitamin D (calcitriol), increasing intestinal Ca2+ absorption.