Notes
Bone Remodeling
Sections
homeostatic process
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.
biology 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
Histological Section in Diagram
- 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.
Full-Length Text
- Here we will learn the process of bone remodeling and repair.
- Start a table.
To begin, let's address the homeostatic process of bone remodeling, which regulates calcium blood levels, repairs worn-out bone, and responds to bone stress.
- Draw a bone and a blood vessel.
- Show that osteoblasts form bone from calcium in blood.
- Then, indicate that osteoclasts break down bone and push calcium into blood.
- Now, start a small table.
- List the header: calcium, osteoblasts, osteoclasts.
- Show that low blood (plasma) calcium levels stimulate osteoclast activity and inhibit osteoblast activity.
- Then, indicate that high blood (plasma) calcium levels inhibit osteoclast activity and stimulate osteoblast activity.
- The reabsorbed bone releases calcium into blood.
- As we'll see, PTH (parathyroid hormone) is a key physiologic mediator for bone homeostasis.
- Denote that in osteoporosis, bone resorption exceeds deposition.
Now let's learn the biological process of bone remodeling.
- Begin with osteoblast generation, which are the primary mediators of bone formation.
- We start with osteoprogenitor cell, which are spindle-shaped osteoblast precursors.
- As we learn in the bone growth tutorial, they are funneled into ossification centers for linear bone growth and they line both the periosteum and the endosteum for appositional bone growth.
- Below the osteoprogenitor cell, draw a pair of active osteoblast cells sitting on a slab of bone matrix.
- Indicate that bone matrix comprises an inorganic component: hydroxyapatite and an organic component: osteoid.
- Denote that 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
- And they mediate osteoclastogenesis (the formation of osteoclasts) via M-CSF (macrophage colony stimulating factor) and RANKL with inhibition by osteoprotogerin.
- Show that members of the (bone morphogenetic protein) BMP family and also transforming growth factor stimulate the differentiation of osteoprogenitor cells to become osteoblast cells.
- Then, indicate that the osteoblasts have cytoplasmic processes, which allow for inter-cellular communication through gap junctions.
- Then, show that the active osteoblasts have well-developed rough endoplasmic reticula and Golgi complexes, and draw their nuclei.
- Now, a lacuna with an osteocyte inside.
- Denote that osteoblasts become osteocytes when surrounded by bony matrix.
- The cytoplasmic processes persist and continue to form gap junctions between cells via canaliculi (which we learn about in the histology of bone tutorial).
- A prominent histologic feature of osteocytes is nuclear heterochromatin.
Next, let's address osteoclastogenesis: the generation of the osteoclast.
- Indicate that the osteoclast precursor is a monocyte.
- Then, indicate that Parathyroid hormone (PTH) and Vitamin D stimulate osteoblasts to secrete factors that promote osteoclastogenesis.
- First, show that osteoblasts produce M-CSF (macrophage colony stimulating factor) stimulation, which stimulates the monocyte proliferation of monocytes, which later fuse into multinucleated PREosteoclasts (we'll see that these nuclei can be as robust as 30 nuclei in a single osteoclast).
- Then, show that 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.
- Next, show that to regulate osteoclast differentiation, osteoblasts release osteoprotegerin, which binds RANKL and inhibits its binding to the RANK receptor.
- Remember that RANKL is a form of osteoprotegerin ligand and thus, osteoprotegerin, itself, can bind it.
- Finally, draw an active osteoclast, which resorbs bone.
- First, draw a dome-shaped osteoclast; along its base, draw a ruffled border as a wavy line, which is the site of active bone resorption.
- Next, draw a Howship lacuna in the surface of bone.
- Show the subosteoclastic compartment beneath the ruffled border (although some texts refer to the Howship lacuna synonymously with the subosteoclast compartment).
- Within the osteoclast, indicate that 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.
- Next, show that actin fibers attach the edge of the cell to the bony surface, which forms the sealing (aka clear) zone of the osteoclast.
- Indicate that osteopontin promotes osteoclast adhesion in this zone.
- Now, indicate that the cytoplasm contains:
- Numerous nuclei.
- Acidophilic vesicles, which are key to the osteoclasts ability to degrade bone – the protons are generated by carbonic anhydrase II.
- Show that these vesicles release hydrogen ions into the subosteoclastic zone that can reduce the pH to as low as ~4.5 to solubilize mineralized bone.
- And show that the cytoplasm is also rich in mitochondria.
- Lastly in our diagram, include a calcitonin receptor on the surface of the osteoclast because this hormone, which the C (clear) cells of the thyroid produce regulates mineral metabolism and bone remodeling through the inhibition of osteoclast activity.
Now, let's look at osteoblasts, -cytes, and -clasts in histological section.
- Identify some typical bony matrix.
- Identify an osteoblast on its surface.
- Identify an osteocyte trapped in the bony matrix.
- Then, encircle some multinucleated osteoclasts in their Howship lacunae – we can see the remarkable degradative effects of the osteoclasts in this section.