Bone Cell Biology - Lough Flashcards
What functions are served by bones?
Structural support
Housing of bone marrow
Calcium/phosphate reservoir
What percentage of bone is inorganic (by mass)?
What mineral largely comprises it?
70%
Hydroxyapatite
What name refers to the organic component of bone matrix? Why does it stain red?
Osteoid
Type I collagen is Acidophilic. (remember, bONE has type ONE collagen)
What two genes are unique to osteoblasts, and what are their functions?
Cbfa-1/Runx2: “Master” transcription factor (absence = dysostosis).
Osteocalcin: Matrix glycoprotein that facilitates Ca2+ deposition.
What are BMPs?
Bone Morphogenetic Proteins, members of the TGFβ superfamily which activate osteoblast differentiation.
How long-lived are osteocytes? Describe their location/distribution.
25yr half-life
They occupy lacunae between lamellae within osteons. They communicate via canaliculi (house cytoplastic processes, gap junctions)
How are osteoclasts formed? Describe their structure and distribution.
Formed from macrophages that fuse together (multinuclear!)
Found in “Howship’s Lacunae”, with ruffled borders forming a microenvironment within the matrix.
What is the effect of PTH on osteoclasts? Describe how this can impact serum calcium levels.
PTH activates lysosomes, which dump H+ and cathepsin-K to resorb the bony matrix. This results in increases in serum calcium.
Which bony cells are found in the periosteum? The endosteum?
Osteoblasts are found in both. Osteoclasts are mostly found in the endosteum. Osteocytes are buried in lacunae within the bone matrix.
Describe the distribution of compact vs spongy bones in flat and long bones.
In flat bones, spongy bone is surrounded by plates of compact bone.
In long bones, the same is true as a cylinder (diaphysis), with caps of compact bone at either end (epiphyses).
What is the name for a canal that travels perpendicular to the length of the bone?
Volkmann’s canal.
Distinguish between endochondral ossification at the diaphysis and epiphyses of a long bone.
At the diaphysis, osteoblasts invade calcified cartilage and lay down osteoid. Bone laid down under periosteum = increase in diameter.
At the epiphyses, chondrocytes proliferate and produce cartilaginous matrix. This is replaced with osteoid by osteoblasts, resulting in an increase in length.
Describe the pathway by which sex hormones (say, during puberty) can promote increase in bone length.
Sex hormones act on the pituitary to promote growth factor, which activate the liver to produce somatomedin/IGF-I, which stimulates chondrocytes.
Which types of collagen can be found at the site of endochondral ossification?
Collagen I (from osteoblasts)
Collagen II (from chondrocytes)
Collagen X (calcified; from chondrocytes)
Summarize the process of fracture repair.
- Macrophages remove debris.
- Chondrocytes form a hyaline cartilage callus.
- Osteoblasts replace it with a bony callus.
- The primary bone is replaced by lamellar, secondary bone.
Distinguish between the pathophysiologie of Osteopetrosis, Osteoporosis, and Paget’s Disease.
Osteopetrosis results from deficient osteoclast activity.
Osteoporosis results from excessive osteoclast activity.
Paget’s disease results from overactive osteoblasts AND osteoclasts.
Osteoporosis
Where are fractures most common?
What are some simple preventative measures?
How is it monitored/screened?
Osteoporosis
At the wrist, hip, and spine.
Treat with Ca2+ & Vitamin D supplements, and resistance exercise.
Screen with bone mineral density assays (yields a “T-score”).
What signals are required for osteoclast production?
What role does OPG play here?
M-CSF to induce macrophage proliferation, and RANK-L on stromal cells to trigger their differentiation to osteoclasts.
OPG or osteoprotegerin, inhibits RANK (the receptor).
Summarize hormonal control of osteoblast and osteoclast activity.
Osteoblasts are inhibited by leptin, but induced by BMP and intermittent PTH.
Osteoclasts are inhibited by calcitonin and OPG, but induced by RANK-L or continuous PTH.
Describe some drugs used (or planned) to treat osteoporosis.
PTH 1-34 (“Forteo”) given in spikes to promote osteoblast activity.
SERMs to replace deficient estrogen signaling.
Bisphosphonates (eg Boniva)
Calcitonin
(experimental) OPG, CBFA-1, or adhesion inhibitors.
What are the (3) chief components of the osteoid?
- Collagen I
- proteoglycans
- osteocalcin (glycoprotein) -> promotes hydroxyapatite formation
What type of collagen is found in hyaline cartilage?
Type II collagen
What type of collagen is found in bone?
Type I collagen
What is osteomalacia?
Softening of the bone tissue caused by deficient mineralization
What is Rickets?
Pediatric osteomalacia
What disease resulting in excessive loss of bone mass features hypernucleated osteoclasts?
Paget’s Disease
Name the lysosomal enzyme released by osteoclasts that is responsible for the breakdown of collagen in bone resorption?
Cathepsin-K
Name (2) synonyms for spongy bone
Cancellous
Trabecular
Name the canal type that generally runs parallel to the long axis of bone
Haversian canal
Primary (woven) bone is primarily found in what processes?
Fetal development
Repair
Name and describe the (5) zones of the epiphyseal plate
- Reserve cartilage
- Zone of proliferation (induced by IGF-I)
- Zone of hypertrophy: hollowed out area responsible for 20% of fractures
- Zone of calcification: calcified cartilage zone with collagen X (basophilic)
- Zone of ossification: deposition of collagen I by osteoblasts (eosinophilic)
Describe the process of osteoclast production
Stromal cells in bone marrow are induced by PTH to secrete 3 factors that regulate osteoclast formation:
- M-CSF (macrophage colony stimulating factor): induces macrophage proliferation
- RANK-L (receptor for activator of nuclear factor-kb ligand): induces macrophage differentiation/fusion into osteoclasts
- OPG (osteoprotegerin): RANK-L receptor antagonist (i.e. antagonizes macrophage differentiation)
What is a T-score (for bones)?
Expression of bone marrow density (BMD): the T-score is the number of standard deviations below healthy normal BMD
What is α5ß3?
A protein expressed by osteoclasts along the margins of the ruffled border that helps seal and form the Howship’s lacuna (resorptive pit microenvironment)
May be a promising drug target in the treatment of osteoporosis
Drugs: describe teriparatide (PTH 1-34)
Produces spikes of PTH level, favoring osteoblast production
Used in clinical management of osteoporosis, especially at T-score < -2.5 where anti-resorptive drugs become ineffective
Name (3) anti-resorptive (anti-osteoclast) drugs used in the treatment of osteoporosis
SERMs (selective estrogen receptor modulators) -> raloxifene
Bisphosphonates: ibrandronate (Boniva)
calcitonin
What is ibandronate?
bisphosphonate drug, used as an anti-resorptive (anti-osteoclast) in the treatment of osteoporosis
Marketing name: Boniva
What is raloxifene?
A SERM (selective estrogen receptor modulator) drug used as an anti-resorptive (anti-osteoclast) in the treatment of osteoporosis
Name an anabolic drug that produces PTH spikes designed to promote osteoblast production in bone
teriparatide (PTH 1-34)
Marketing name: Forteo
