Bone Remodeling
bone remodeling
homeostatic process of bone remodeling
Key Functions
- Regulates calcium blood levels
- Repairs worn-out bone
- Responds to bone stress
Actions
- Osteoblasts form bone from calcium in blood and that osteoclasts break down bone and push calcium into blood.
- LOW blood (plasma) calcium levels stimulate osteoclast activity and inhibit osteoblast activity.
- HIGH blood (plasma) calcium levels inhibit osteoclast activity and stimulate osteoblast activity.
- Reabsorbed bone releases calcium into blood and PTH (parathyroid hormone) is a key physiologic mediator for bone homeostasis.
Clinical Correlation: In Osteoporosis, bone resorption exceeds deposition.
The biological process of bone remodeling
Osteoblast Generation
Osteoblasts are the primary mediators of bone formation.
Osteoprogenitor cells
- Spindle-shaped osteoblast precursors.
- They are funneled into ossification centers for linear bone growth.
- They line both the periosteum and the endosteum for appositional bone growth.
Osteoblasts
- Lie along bone matrix. Bone matrix comprises an inorganic component: hydroxyapatite and an organic component: osteoid.
- Osteoblasts are critical to bone formation, they:
- Secrete osteoid (the organic (unmineralized) portion of bone – ie, the type 1 collagen fibers and ground substance).
- Mineralize hydroxyapatite (the hydroxylated calcium and phosphate component of bone) via osteocalcin and osteonectin
- Mediate osteoclastogenesis (the formation of osteoclasts) via M-CSF (macrophage colony stimulating factor) and RANKL with inhibition by osteoprotogerin.
- Stimulation of osteoprogenitor cell differentiation:
- Members of the (bone morphogenetic protein) BMP family
- Transforming Growth Factor Beta
- Cellular components of osteoblasts include:
- Cytoplasmic processes, which allow for inter-cellular communication through gap junctions.
- Well-developed Rough Endoplasmic Reticula, Golgi complexes, and prominent Nuclei.
Osteocyte
- Lie within lacuna
- Osteoblasts become osteocytes when surrounded by bony matrix.
- The cytoplasmic processes persist and continue to form gap junctions between cells via canaliculi.
- A prominent histologic feature of osteocytes is nuclear heterochromatin.
osteoclastogenesis
The generation of the osteoclast.
Osteoclast precursor: Monocyte
- Parathyroid hormone (PTH) and Vitamin D stimulate osteoblasts to secrete factors that promote osteoclastogenesis.
Osteoblasts stimulate osteoclastogenesis via:
- M-CSF (macrophage colony stimulating factor) stimulation, which stimulates the monocyte proliferation of monocytes, which later fuse into multinucleated Pre-Osteoclasts (we'll see that these nuclei can be as robust as 30 nuclei in a single osteoclast).
- RANKL (an osteoprotegerin ligand, which is in the tumor necrosis factor family (TNF family)) binds to the RANK receptor on the multinucleated osteoclast to stimulate differentiation from pre-osteoclast to osteoclast.
Osteoblasts regulate osteoclastogenesis via:
- Osteoprotegerin, which binds RANKL and inhibits its binding to the RANK receptor. RANKL is a form of osteoprotegerin ligand and thus, osteoprotegerin, itself, can bind it.
Osteoclast: Active State
The dome-shaped osteoclast resorbs bone.
- Along its base, lies a ruffled border (which appears as a wavy line).
- The Howship lacuna lies in the surface of bone.
- The subosteoclastic compartment lies beneath the ruffled border
Note that some texts refer to the Howship lacuna synonymously with the subosteoclast compartment).
- The region above the ruffled border is the vesicular zone; vesicles for exocytosis and endocytosis reside here. It is the exocytosis of calcium and phosphorous to the extracellular environment of the osteoblast that promotes crystal nucleation of bony matrix.
- Actin fibers attach the edge of the cell to the bony surface, which forms the sealing (aka clear) zone of the osteoclast. Osteopontin promotes osteoclast adhesion in this zone.
- Osteoclast cytoplasm contains
- Numerous nuclei.
- Acidophilic vesicles, which are key to the osteoclasts ability to degrade bone – the protons are generated by carbonic anhydrase II. These vesicles release hydrogen ions into the subosteoclastic zone that can reduce the pH to as low as ~4.5 to solubilize mineralized bone.
- The cytoplasm is also rich in mitochondria.
- Calcitonin receptors lie on the surface of the osteoclast. Calcitonin is produced by the C (clear) cells of the thyroid. It regulates mineral metabolism and bone remodeling through the inhibition of osteoclast activity.
Histological section
- We see typical bony matrix.
- An osteoblast on its surface.
- An osteocyte trapped in the bony matrix.
- Multinucleated osteoclasts in their Howship lacunae. We can see the remarkable degradative effects of the osteoclasts in this section.