Bones Flashcards
4 functions of bone
- Provides infrastructure for the body
- Contains bone marrow components: erythroid, myeloid, and stem cells
- A specialized mineralized ECM connective tissue
- Storage of Calcium and Phosphate.
Which cell type is responsible for bone resorption?
Osteoclasts
Which hormone induce osteoclast action and which hormone antagonizes osteoclast action?
PTH induces osteoclasts for bone resorption;
Calcitonin inhibits osteoclasts for bone resportion
What is two major components of bone?
cells and matrix
what are the major cell types within bone?
Where are they located?
Osteoclasts; (endosteum)
Osteocytes (within lacunae inside lamellae) in the main bone portion incased in periosteum and endosteum
Osteoblasts; mostly in periosteum; some in endostum
Two components of bone matrix?
What percentage are they?
Specific composition of each of the 2 major components?
Inorganic component (70%): hydroxyapetite (calcium and phosphate) (99%) of body's calcium. Organic component/ Osteoid (30%): type 1 collagen (acidophilia), proteoglycans (not a lot), glycoproteins (mostly protein; some surgars)--> promote calcification
Comparing bone vs Hyaline Cartilage on the following dimensions: Mineral Water Collagen Neurovascular structures
Hyaline cartilage: no mineral, 75% water, type II collagen, no neurovascular structures
Bone:70% minerals (cal and phosph), 25% water, Type I collagen, has neurovascular structures
Glycoproteins within bone matrix promote what?
What are the major proteins?
Glycoproteins promote calcification of bone.
Major proteins are Osteocalcin (ONLY FOUND IN BONE), sialoprotein, osteopontin
What makes bones hard?
Hydroxyapetite and Type I collagen.
(for hydroxyapetite presence… need osteocalcin.
Osteoblasts
- What type of cells are they?
- What’s their major function?
- They’re under control of which factors?
- Which two gene products are specific to osteoblasts?
Osteoblasts are fibroblasts.
Their major function is to SYNTHESIZE the bone ECM
They’re under control of BMPs.
Two gene products: Cbfa-1 which is the “master gene” for bone development in embryos (knockouts have cartilaginous bones).
Osteocalcin is the other osteoblast specific product
What is Osteoid?
What is it synthesized by?
Where does it deposit?
The organic component of bone matrix (type I collagen, proteolycans; glycoproteins)
Synthesized by osteoblasts; deposited where hydroxyapetite is.
Clinical Significance of Tetracycline in bones?
Tetracycline intercalates into ECM of bones–> autofluorescence–> can monitor apposition growth.
Osteomalacia
What’s the defect?
Calcification is impaired
Osteitis Fibrosa Cystica
What’s the defect?
rapid osteoclast destruction of bone matrix as it is made.
Osteocytes Main function Half life Structure in bone What is different about osteocytes vs chondrocytes in terms of structure
Main function is to MAINTAIN the bone ECM
- T1/2=25 years
- Single osteocytes occupy single lacunae, which are embedded in lamellae, Cytoplasmic processes protrude from the lacunae via “canaliculi” to allow osteocytes to touch and form gap junctions for neurishment.
Osteoclasts Main function Cell origin/cell morphology where do they reside? What activates it? What inhibits it?
to breakdown and remodel bone ECM
- they are fused macrophages
- They are polarized cells with with one ruffled border that attaches to and degrades bone minerals.
- They reside in “Howship’s lacunae”
- Activated by PTH; inactivated by calcitonin
Type I collagen
Acidophilic or basophilic?
Acidophilic
Bone formation process is completed by
after osteoblasts make osteoid (type I collagen, proteoglycans, glycoproteins)… Osteocalcin mediates calcium deposition into osteoid… allowing for weight bearing.
How does PTH affect bone?
What’s the mechanism? Specific
PTH activates osteoclasts to release LYSOSOMES–>Cathepsin-K–> release in to the microenvironment…
Acid–> released into microenvironment
Paget’s Disease
- patient population
- mechanism
- what cell type is affected? what’s the morphology of the cells?
affects adults over 40
abnl osteoclasts –> high remodeling rate… leading to an over abundance of weak immature bone “Primary/woven bone”;
largely increased number of nuclei (normally 7 nuclei per osteoclast)
Osteoporosis (general)
- patient population
- How to prevent
- How to screen
- Therapeutic targets (theoretical)
Overactive osteoclasts
- ->hollow fragile bones
- post menopausal women (via 2% bone loss per year)
- prevention with Calcium and Vitamin D supplement +weight bearing exercises
- Screening of (bone mineral density) BMD (g/cm^2)
- compare BMD to young subjects every 2-5 years
- therapeutic targets: iincrease osteoblasts and decrease osteoclasts
Two general parts of a piece of bone? upon cross section
Upon microscopic analysis what is different?
Cortical/Compact bone (dense; no cavitation)
Spongy/ Trabecular/cancellous bone (has cavitation)
-Nothing is different microscopically.
Flat bones
Example; structure
calvaria bones; compact bone surrounding a “diploe” of spongy bone
Long bone
Example;
Structure
femur;
diaphysis, metaphysis, and epiphysis
What is an osteon
What is all within an osteon?
What is in the inner most lamella?
an osteon is a concentric tube of lamellae
Within an osteon there’s layers of lamellae; 1 osteocyte resides in each lacunae;
In the inner most lamella there’s the haversian canal, which holds blood vessels, nerves, and lymph
What are two types of canals within bone? which one is horizontal and which one is vertical?
What is within these?
Haversian canal: vertical
Volkmann’s canal: horizontal
contents: artery, vein, lymph vessels, and nerves
What is immature bone called? (2 names)
What is mature bone called? (2 names)
What is the distinction?
- primary bone or woven bone
- lamellar bone or secondary bone
Difference is immature bone do not have lamellae
Two ways of bone development
- Intramembranous: Osteoblasts deoposit osteoid onto mesoderm
- endochondral: osteoblasts deposit osteoid onto cartilage (long bones in embryo and s/p fx)
Endochondral bone development
-diaphysis and epiphysis what’s different?
bone forms on hyaline cartilage
- at diaphysis: osteoblasts invade calcified catilage and secret osteoid
- THIS IS CALLED OSSIFICATION - at the epiphysis: same process but leaves articular cartilage and epiphyseal growth plate.
Hormonal stimulation process for long bone growth
Sex steroid hormones–> pituitary stimulation–> release of GH AKA somatotropin–> liver–>somatomedin (IGF1)–> epiphyseal plate stimulated in the “zone of proliferation”
4 zones of the epiphyseal growth plate
Zone of proliferation: proliferation upon IGF1 (somatomedin) stimulation
Zone of Hypertrophy: 20% of fractures occure here because it’s relatively hollow in nature
Zone of calcification: basophilic–occupied by calcified cartilage with abundant (TYPE X cartillage)
Zone of Ossification: eosinophilic: deposition of type I collage by osteoblasts
Process of fracture repair
- Macrophages remove debris
- Chondroblasts secrete callus (hyaline catillage)
- Osteoblasts replace hyaline cartillage with “bony callus”…primary bone
- primary bone is replaced by secondary bone
Methods of Bone Tissue Engineering in cases that need “grafting of bone”
GF: such as BMP 2 and BMP 7
Stem cells: mesenchymal stem cells (MSC) will mature in to osteoblasts
one or both of the above are implanted onto biodegradable matrix made from type 1 collagen.
Osteopetrosis
dense heavy bone; osteoclasts lack ruffled borders…so cannot degrade bones
Osteoclast activity regulated by Bone stromal cells
-How does it work?
Bone stromal cells produce:
M-CSF, RANKL, and OPG (osteoprotegerin)
which act on macrophages that induce or inhibit action of osteoclasts
M-CSF-where is it from, what does it do
From stromal cells
macrophage colony stimulating factor
Induces macrophage proliferation
RANK L: receptor for activator of nuclear factor kB ligand
where is it from what does it do?
from stromal cells
induces macrophage differentiation to osteoclasts
OPG/ Osteoprotegerin
where is it from?
what does it do?
from stromal cells of bone
antagonizes RANK L receptors, so that macrophages cannot differentiate into osteoclasts.
Alpha5beta3
What is it?
What does it do?
what if it’s not present?
It attaches osteoclasts to bone
if blocked…then osteoclasts cannot bind and degrade bome.
Osteoblasts Vs Osteoclasts
Inducers, inhibitors
Osteoblasts:
Induced by BMP
Inhibited by leptin
Spikes in concentration of PTH levels
Osteoclasts:
Induced by RANK L
Inhibited by Calcitonin, and osteoprotegerin
constant PTH levels
Osteoporosis
Two therapeutic drug types?
Anabolic drugs (proosteoblasts)
-PTH 1-34 “Teriparatide”: to mimic spikes in PTH
When T score is less than -2.5 in BMD antiresorptive drugs will not work… so this is drug of choice…
Antiresorption drugs (antiosteoclasts)
- SERMs (selective estrogen receptor modulars): raloxifene
- Bisphosphonates: Iabndronate (boniva)
- Calcitonin
Other methods:
- OPG
- anti alpha5beta3
- CBFA-1 (anabolic)
