Term
| What are the 4 basic components of cartilage matrix produced by chondroblasts and what are their primary functions? |
|
Definition
1) Collage (40-70% of organic molecules)- resist stretching
2) Elastin- in elastic cartilage
3) Ground substance-
Aggrecan- hydrated proteoglycan that resists compression
Chondronectin- glycoprotein that links cartilage to matrix, binding collagen type 2 and integrins on condrocytes
Condrocalin- calcification of hyaline cartilage during bone formation
4) Water- 80% wet tissue weight that contributes to rigidity. |
|
|
Term
After releasing matrix, chondroblasts become chondrocytes as they get stuck in ECM. What are the cavities called where these cells die?
How do they relate to territorial matrix? |
|
Definition
Lacuna
Lacuna are surrounded by dark-staining young tissue patches containing sulfated glycosaminoglycans called "territorial matrix." |
|
|
Term
| What is the importance of the cell nest/isogenous group in cartilage tissue? |
|
Definition
| After releasing matrix, chondrocytes can still divide a couple of times allowing for interstitial growth in existing tissue. |
|
|
Term
| How can appositional growth occur in cartilage? |
|
Definition
| The chondrogenic layer of perichondrium surrounding cartilage contains progenitor cells that can develop into chondroblasts, |
|
|
Term
| How do cartilage cells obtain vascular supply? |
|
Definition
| Only vasculature is located in fibrous perichondrium, and nutrient and gas exchange takes place by diffusion through hydrated cartilage. |
|
|
Term
What type of highly hydrated cartilage contains dense, collagen type II fibers with very dense aggrecan populations?
Where would you find this cartilage? |
|
Definition
1) Hyalin Cartilage
2) Costal cartilages, articular surfaces, epiphyseal plates, respiratory tract, embryonic skeleton |
|
|
Term
1) What type of cartilage contains elastin, collagen type II and a medium amount of aggrecan?
2) Where is this cartilage found? |
|
Definition
1) Elastic
2) External ear, eustachian tubes, epiglottis |
|
|
Term
1) What type of highly hydrated cartilage contains large, thick collagen type I fibers and a medium amount of ground substance, but is LACKING a perichondrium?
2) Where is this cartilage found? |
|
Definition
1) Fibrocartilage
2) Articular discs of the knee, IV discs, pubic symphysis, ends of tendons and ligaments at attachment points. |
|
|
Term
| Why is there such a notable loss of compressibility in the bones of patients suffering from osteoarthritis? |
|
Definition
Decreased sulfated proteoglycan content!
Cant hydrate the tissue, which decreases compressibility and nutrient supply. |
|
|
Term
| Osteoblast cells are important for matrix production and bone mineralization. How do alkaline phosphatase secretions relate to this? |
|
Definition
Hydrolyze monophosphate esters to free up Pi for mineralization.
Recall- these calls also produce cartilage I and proteoglycans for matrix production. |
|
|
Term
What is the action of vitamin D3 on osteoblast activity?
What about PTH? |
|
Definition
1) Binds D3 receptors to increases collagen 1 and alkaline phosphatase synthesis.
2) begins osteoclast activation and leads to the production of mCSF, which binds RANK during osteoclast maturation. |
|
|
Term
| What makes up the osteoid component of bone (important for tensil strength/stains eosinophilic)? |
|
Definition
1) Collagen type I
2) Low proteoglycan Ground Substance with
Osteonectin (links collagen to matrix)
Osteocalcin (binds calcium for osteoid mineralization)
Osteopontin (binds osteoclast integrins to seal off digestize zone during turnover)
3) Minerals- calcium and phosphate that ppt as hydroxyapeptite which forms crystals that bind collagen I (diffusion is limited in osteocytes because of dense matrix).
4) Water- 8% weight |
|
|
Term
| Since the dense bone matrix of osteocytes prevents nutrient diffusion, how do osteocytes obtain vascular supply? |
|
Definition
| Cytoplasmic extensions that travel through "canaliculi" connect adjacent osteocytes to communicate with blood vessels. |
|
|
Term
| Why is there no interstitial growth of matrix in bone, but there is in cartilage? |
|
Definition
| Dense bone matrix prevents it. Appositional growth can occur, however, in osteogenic periosteum. |
|
|
Term
| Where is Endosteum found? |
|
Definition
Remember, this is connective tissue and osteoprogenitor cells that are sites for appositional growth.
Found lining marrow cavity, inside haversian canals and on the outer surface of spongy bone trabeculae. |
|
|
Term
| How are osteoclasts able to digest bone? |
|
Definition
1) At Howship's lacunae (digestive zones), actin links osteoclasts to transmembrane integrins that are connectived to osteopontin within the bone matrix.
2) Low pH is maintained by cytoplasmic carbonic anhydrase, which generates H+ ions delivered to digestive zones via ATP driven proton-pumps (cytoplasm is full of mitochondria).
3) pH 4.5 HCl digests bone, and secreted lysosomal hydrolases and metalloproteinases (activated at low pH) digest collagen and proteoglycan components of osteoid. |
|
|
Term
| Explain how calcitonin and PTH regulate bone resorption. |
|
Definition
1) When plasma calcium is high, Calcitonin binds to osteoclasts, inhibiting their action and preventing resorption.
2) When plasma calcium is low, PTH binds osteoblasts which causes mCSF release, RANK ligand synthesis and decreased osteoprotegrin synthesis.
- release mCSF (increasing monocyte production in bone marrow, which will become osteoclasts and macrophages)
- increase RANK ligand synthesis which will bind RANK on osteoclast progenitor and stimulate differentation.
- block synthesis of osteoprotegrin, which usually blocks RANK ligand. |
|
|
Term
| Explain how the organization of the Haversion system enables vascular supply to dense bone matrix |
|
Definition
Short-Projections from osteocytes in lamellae enter Haversian systems through canaliculi. Haversian canals are separated by cement lines and are interleaved perpendicularly by Volksmann's canals.
Explanation
1) Haversion canal runs in parallel to the length of a long bone and contains vessels and a nerve (lined with endosteal cells)
2) Canal is surrounded by Lamellae rings (no isogenous groups) containing osteocytes and collagen I bundles.
3) Osteocyte projections extend from lacunae through canaliculi to connect neighboring cells via gap junctions and enable nutrient exchange in Haversion canal.
4) Perpendicular Volkmann's canals provide access for vasculature to enter compact bone from periosteum and endosteum.
5) Cement lines separate haversian lines and are indicators of bone turnover. |
|
|
Term
| What is the biggest difference between Cancellous, trabecular (spongy) bone and solid bone? |
|
Definition
They lack Haversion systems and have limited diameters of 0.2mm.
Osteocytes lie within 0.1mm of each other and still piggyback with each other via canaliculi. |
|
|
Term
| Why does Osteomyelytis frequently occur at metaphyseal veins in children? |
|
Definition
Sluggish blood flow and paucity of phagocytes favor growth of bacteria.
Recall; since bones are vascularized, they are susceptible to blood-borne, hematogeneous infections, as well as contiguous infections via the periosteum. |
|
|
Term
1) Distinguish between intramembranous and endochondrial ossification.
2) What features are the same for both? |
|
Definition
1)
Intramembranous- bone osteoid is secreted by new osteoblasts as mass of embryonic mesenchyme (occurs in embryonic mesenchyme because of BMP influence)
Endochondrial- Hyalin cartilage miniature of "bone" called an enlarge becomes bone
2)
Both first lay down primary bone with randomly oriented collagen fibers
In both cases, primary bone is digested and replaced by secondary bone consisting of organize collagen fibers.
Both are examples of "appositional growth" (bone cant grow any other way!) |
|
|
Term
1) Which bones arise via intramembranous ossification?
2) Which bones arise via endochondrial ossification?
3) Which bones arise via both? |
|
Definition
1) Flat bones of skull, outer sheath of long bones, clavicle.
2) Bones of extremities, VC, pelvis
3) Long bones of body (length via endochondral and width via intramembranous) |
|
|
Term
| How do the different elements of the Diaphysis (shaft) develop? |
|
Definition
1) Periosteal bone collar (intramembranous)-
BMPs cause progenitors to differentiate into osteoblasts, which secrete osteoid that becomes mineralized to create outer shaft.
2) Primary center of ossification (endochondral)
SHORT BMPs hypertophy chondrocytes, which release VEGF that causes "periosteal bud" to turn into osteoblasts after entering the bone collar.
Explanation
BMPs transform chondrocytes of enlarge into hypertrophied cells that are mineralized by hydroxyapatite. These cells die
VEGF produced by hypertrophied cells causes "periosteal bud" (w/ blood vessels and osteoprogenitor cells) to migrate through bone collar where they differentiate into osteoblasts.
3) Length
Chondrocytes above and below primary center divide and enlarge in length (primary center expands and center is digested and replaced with myloid (blood-forming) tissue). |
|
|
Term
| How does the Epiphysis develop? |
|
Definition
Secondary centers of ossification at distal and proximal epiphyses turn cartilage into bone (similar process to primary center)
Hyaline coats are maintained at ends to act as articular surfaces. |
|
|
Term
| Explain the development of an epiphyseal growth plate. |
|
Definition
Primary and secondary centers of ossification eventually meet, but sandwiched layer of cartilage remains (i.e. growth plate) from which the bone can be lengthened.
Increases in length occur at the "Zone of Proliferating Cartilage" |
|
|
Term
| How does the "Zone of Hypertrophied Cartilage" in the epiphyseal growth plate regulate bone turnover? |
|
Definition
Hypertrophied chondrocytes express Vit D3 receptors, which cause the synthesis of
1) Collagen X- related to collagen IV. Serves as nidus for ppt of mineral of bone while preserving porosity
2) Alkaline Phosphatase- liberates organic Pi
3) Chondrocalin- binds calcium
4) Collagenase- cleaves collagen II of hyaline cartilage
5) VEGF- attracts bone and blood precursor cells
As calcium (bound by chondrocalin) and Pi (via alkaline phosphate) levels rise, hydroxyapatite crystals ppt on collagen X. |
|
|
Term
| What feature defines the "zone of resorption and ossification" in the epiphyseal growth plate? |
|
Definition
| Angiogensis and migration of newly differentiated osteoblasts and osteoclasts (these cells are attracted to this zone by VEGF secreted by hypertrophied condrocytes). |
|
|
Term
| Why are spongy bones such as vertebral bodies and the neck of the femur damaged most quickly in osteoporosis? |
|
Definition
Spongy bone turns over 25% each year (compact bone is only 3-4%). In osteoporosis, there is decreased growth, but resorption rate via osteoclasts remains the same!
You simply lose spongy bone faster and it is not being re-synthesized! |
|
|
Term
| What "nonpharmacological" therapies for osteoporosis exist? |
|
Definition
1) Vitamin D (more for postmenopausal women)
2) Excercise 30 min, 3x/week
3) STOP SMOKING |
|
|
Term
| How do Bisphonates such as alendronate act to treat osteoporosis |
|
Definition
Bind calcium hydroxyapatite and decrease bone resorption by blocking function and survival of osteoclasts.
DO NOT FLOCK FORMATION OF OSTEOCLASTS
Work OK in the short term, but after 1 year bone growth slows as well and after 5 years, necrosis is observed. |
|
|
Term
| How do SERMS such as raloxifene act to treat osteoporosis |
|
Definition
Inhibit bone resorption by binding to estrogen receptors and acting as estrogen agonosts which promote apoptosis of osteoclasts (TGF-b mediated?).
Risk include thromboembolisms. |
|
|
Term
| How does Calcitonin act to treat osteoporosis |
|
Definition
Synthetic polypeptide from salmon (40X greater affinity for receptor than human version).
Causes apoptosis of osteoclasts and shuts down bone resorption (5 -years post menopause to prevent pain from osteoporotic fracture) |
|
|
Term
| How do Anti-RANK ligands such as denosumab act to treat osteoporosis? |
|
Definition
Denosumab is a human monoclonal antibody against the RANK ligand, which prevents the maturation of osteoclast precursors.
Remember, RANK/RANK-L cascade is also involved in immune cells, so treatment can lead to infections. |
|
|
Term
| How do Cathepsin K inhibitors act to treat osteoporosis? |
|
Definition
| Cathepsin is a proteinase that is released by osteoclasts to resorb bone organic molecules. Also used to treat metastatic bone cancer. |
|
|
Term
| What is Teriparatide and what is it used for? |
|
Definition
Only drug that BUILDS BONE
It stimulates osteoclast activity (which is wierd), but has the net effect of stimulateing osteblastsa and the synthesis of new bone osteoid.
synthetic peptide that is the first 34 AA of the N-terminus of PTH.
Only works for 6 months, before it shifts towards resorption (only used for patients with most severe bone fractures, a history of fractures) |
|
|
