Bone and Cartilage Flashcards
(82 cards)
1
Q
Endochondral ossification make up the bonesof ?
A
- axial skeleton
- appendicular skeleton
- base of skull
2
Q
Process of bone formation in endochondral ossification?
A
- Cartilaginous model of bone is first made by chondrocytes
- Osteoclasts and osteoblasts later replace this with woven bone—>
- then remodel to lamellar bone
3
Q
Membranous ossification make up which bones?
A
Calvarium and facial bones (skull).
4
Q
Process of bone formation in membranous ossification?
A
- Woven bone is formed directly without cartilage.
- Later is remodeled to lamellar bone
5
Q
- Osteoblasts function?
- Osteoblasts differentiate from?
A
- Builds bone by secreting collagen and catalyzing mineralization in alkaline environment via ALP
- Differentiates from mesenchymal stem cells in periosteum
6
Q
- Osteoclasts function?
- Osteoclasts differentiate from?
A
- Dissolves bone by secreting H+ and collagenases
- Differentiate from a fusion of monocyte/macrophage precursors
7
Q
Organic matrix is important to strength of bone. What is matrix made up of?
A
- Over 90% collagen fibers
- ground substance
- mainly proteoglycans, chrondroitin sulfate and hyaluronic acid
8
Q
Bone composition is 30%__ and 70%__?
A
- 30% matrix
- cells maintain and produce matrix
-
extracellular component of bone
- 35% osteoid (organic)
- 65% mineral (inorganic)- hydroxyapatite
- 70% salts
9
Q
What is the major component of bone salts?
A
- Hydroxyapatite (form of calcium phosphate)
- inorganic
- important in deposition of Ca
10
Q
- Collagen in bong is along lines of?
- Important for?
A
- Along lines of tensional force
- Important to tensile strength
- Has high compression strength so bone resists both tension and compression
11
Q
- Extracellular matrix forms most of what kind of tissue
- What is important to density and deformability of matrix?
A
- Forms bulk of connective tissue
- Hydration is important!
12
Q
What are the functions of ECM?
A
- Provides structure and support
- (holds cells and tissues together)
- Limit movement and migration
- barrier to microorganisms and large molecules
13
Q
- What is the most abundant type of protein in the body, especially which form?
- Found in?
A
- Collagen 1
- found in:
- loose connective tissue,
- bone
- tendons,
- skin
- blood vessels
14
Q
Structure of collagen? What does it need to stabilize it?
A
- Triple helix with repetitive nature
- needs vitamin C to stabilize
15
Q
- Lack of Vitamin C means less stability of __?
- Symptoms of Scurvy?
A
- Less stability of collagen and tissues where it is important
- Skin less stable, blood vessels easily injured, gums less stable so teeth are loose
16
Q
- Collagen IV makes a __ rather than fibrils.
- Important in which structures?
A
- Makes a mesh
- important in basement membranes and basal lamina
17
Q
- Glycosaminoglycans (GAG) are repeating __ units with?
- Which glycosaminoglycan is the backbone of the matrix?
A
- Repeating disaccharide units
-
Hyaluronic acid (just disaccharide units)
- bind HA to proteoglycans
- Negative charges bind positive ions,
- H+ bonds to water to form hydrated gel
- matrix is flexible and acts a filter
18
Q
How is cartilage able to be compressed and deformable/regain shape after pressure is released?
A
- High number of negative charges attract cations,
- create high osmotic pressure water drawn in,
- tension balances at swelling equilibrium
19
Q
Function of fibronectin in the matrix?
A
- Proteoglycans bind to fibronectin (besides HA)
-
Fibronectin binds to integrins in cell membranes
- collagen fibrils cells attached to all matrix components
20
Q
How is bone matrix degraded?
A
- Components (GAG) enter cells by endocytosis and fuse with lysosomes
-
lysosomal hydrolase break these down into sugars and amino acids
- lack of any enzyme will prevent degradation and accumulation of partially degraded material in lysosome
21
Q
- Stem cells in bone respond to ___ from osteoblasts?
- These precursors then become osteoclasts that respond to__ and __?
A
- M-CSF from osteoblasts
- precursors become osteoclasts
- responding to IL-6 and RANKL;
- important in osteoclast regulation and bone remodeling/resorption
22
Q
- Osteoclasts are regulated by __ and __?
- What do osteoclasts release against bone surface?
A
- Cytokine receptors (stimulate resorption)
- Calcitonin (inhibit resorption)
Release H+ ions, phosphotases (TRAP) and lysosomal enzymes
23
Q
- Integrins are?
- What type of signals to they transmit?
A
- Transmembrane proteins (alpha-beta dimers)
- connect to matrix and cytoskeleton
- Pass physical signals across cell membrane
24
Q
Role of matrix maetalloproteinasees (MMPs) in degradation of ECM proteins?
A
-
MMP degrade all ECM proteins (locally)
- Important for migration and remodeling
25
Regulation of MMPs in degredatin of ECM proteins?
* Synthesized with **propeptide** that must be cleaved to activate
* **TIMP** (Tissue Inhibitors of Malloproteinases)
26
On which cells in the bone are the RANK receptor and ligand located?
* RANK ligand on osteoblast/stromal cell
* RANK receptor on osteoclast precursor
* Need RANK and M-CSF (always floating around) to differentiate into osteoclast
27
What binds to the RANK ligand on osteoblast/stromal cells and inhibits it's interaction with RANK receptor on osteoclast precursor cells?
* Osteoprotein (**OPG)** prevents differentiation into osteoclast
* acts as a decoy for RANKL
28
What are other ECM proteins that are not important in bone but are important in skin and other tissue?
* **Laminin**
* Binds collagen to ECM molecules and cell integrins to provide stability
* **Elastin**
* allows blood vessels to deform, lungs to expand and contract without energy
29
Where is elastin found?
Abundant elastic fibers found in:
* smooth muscle endothelium near chondrocytes and fibroblast
30
* Chrondroblasts form from which cells?
* Where are they abundant?
* Form from mesenchymal cells
* Abundant in the perichondrium
31
* Chondrocyte is defined when?
* What do chondrocytes secrete?
* Abundant in?
* Defined when chondroblasts are surrounded by the "matrix" they produce
* Sit in **lacunae**
* Secrete **Type II collagen** and extracellular matrix
* Abudant lipids, glycogen and RER
32
Extracellular matrix ("ground substance") consits of?
* Hyaluronic acid
* glycosaminoglycans
* chondroitin sulfate
* keratin sulfate
It is extremely hydrated
33
* Pericellular matrix has the highest concentration of?
* What type of collagen surrounds each chondrocyte?
* highest [] of sulfated proteoglycans, hyaluronic acid and glycoproteins
* **Type VI** collagen surrounds each chondrocyte
34
What does territorial matrix consist of?
**Type II collagen** and proteoglycans
35
* What parts of the body is comprised of hyaline cartilage?
* What does it serve as?
* Nasal, laryngeal, costal and tracheal cartilage
* Articular cartilage
* **Fetal skeleton**
Serves as shock abosorber
36
What is hyaline cartilage composed of?
* Cells (chondrocytes and chondroblasts)
* Type II collagen fibers (mostly)
* Extracellular matrix
* hyaluronic acid, proteoglycans and water
37
Chondrogenesis:
* Appositional growth?
* Interstitial growth?
* **_Appositional growth:_**
* new cartilage formed from inner surface of perichondrium
* **_Intersitial growth:_**
* new cartilage formed from within cartilage
38
* Where is fibrocartilage found?
* Characterized by?
* Found in:
* intervertebral disk
* menisci of knees
* TMJ
* sternoclavicular joints
* pubic symphis
* Characterized by **great tensil strength**
39
Fibrocartilage is comprised of?
* Chondrocytes and firbroblasts
* **Type I and Type II collagen**
* **less water and proteoglycans** than hyaline cartilage
40
Annulus fibrosis and Nucleus pulposus (intervertebral disk) are made of?
* Annulus fibrosis
* fibrocartilage
* Nucleus pulposes
* Physaliphorous cells and extracellular matrix of ground substance (squishy)
41
* Where is elastic cartilage found?
* Abundant in?
* Characteristics?
* In external ear, epiglottis and auditory tube
* **Abudant type II collagen** and elastic fibers in ECM
* Elastic and pliable
42
What makes articular cartilage different from general hyaline cartilage?
* No perichondrium (contacts bone directly)
* Obliquely oriented collage matrix in transition zone
* Longitudinally oriented collage fibrils in the deep zone
43
T/F:
* Cartilage repairs easily
* False!
* cartilage is not very capable of repair
* **avascular**
44
* What does perichondrium have that relates to repair?
* When damage is repaired what happens to hyaline cartilage?
* Perichondrium has **pluripotent stem cells**
* but type II collage is very stable
* When damage is repaired, hyaline cartilage is converted to mixture of hyaline and fibrous cartilage
* mix of **type I and II cartilage**
* **Damaged cartilage may even be converted to bone (**normal with aging)
45
Lamellar bone
Mature bone with lamellae (overlapping folds)
46
Woven bone?
* Common in?
Developing or immature bone
* **Fetus or fracture**
47
* Compact bone is defined by?
* Where is it found?
* Defined by osteons **(Haversion system)**
* Solid bone found in outer protions of shaft of long bones
48
* Spongy/Cancellous bone found toward?
* Lamellated but no?
* Bony spicules and trabeculae found toward the marrow space and in the metaphyses
* Lamellated but **NO Haversion system**
49
Bone matrix is composed of:
* Organic
* Inorganic
What is in each?
_Organic_:
* **Type I collagen**, proteoglycans, chondroitin sulfate, keratin sulfate, hyaluronic acid
* Multiadhesive glycoproteins
_Inorganic_
* **Hydroxyapatite** (caclium phosphate)
50
Long bone is composed of:
* Periosteum: inner and outer layer
* Sharpey's Fibers
* Lamallae
* _Periosteum_
* _Outer laye_r: collagen fibers and blood vessels
* I_nner laye_r: osteoprogenitor cells and osteoblasts
* _Sharpey's fibers:_
* collagen fibers to the outer circumferential lamellae
* _Lamallae_
51
* In corticol (compact) bone which way do each run? What are they surrounded by?
* Haversian canals
* Volkmann canals
* Haversion canals run **longitudinal**
* ****surrounded by concentric lamellae
* Volkmann canal runs transverse
* transversely connect to Haversion system and to the periosteum
52
* In compact bone where is Endosteum vs. Periosteum?
* What does it contain?
* Osteoprogenitor cells
* osteoblasts
* reticular fibers
53
Where do osteocytes sit?
In lacunae (trapped osteoblasts)
54
Osteoid contain?
**Type I collagen** and proteoglycans
55
Osteoblasts contain abundant RER to produce?
* **Osteocalcin**
* mediates bone mineralization via Ca2+ binding
* **Osteonectin**
* brindges collages and minerals (hydroxyapetite)
* **Alkaline phosphotase**
* **Osteoid**
* secrete Type 1 collagen
* pyrophosphatase
56
Where are osteoclasts multinucleated?
merging of monocytes and macrophage progenitor cells in BM
57
What do osteoclasts secrete?
* **Acid**
* degrade minerals in bone
* **Lysosomal proteins**
* degrade collagen and non collagen proteins
* **Metalloproteinases (MMP)**
* degrade collagen and non collagen
58
Osteoclasts are regulated by?
* **PTH**:
* stimulates **RANKL** on surface of osteoblasts
* RANKL interacts with receptors on surface of osteoclasts and encourage bone resorption
59
Role of pyrophosphate and alkaline phosphate in bone?
* _Pyrophosphate_:
* controls (**inhibits**) mineralization
* _Alkaline phosphotase:_
* neutralizes pyrophosphate
60
* Intramembranous ossification is important for the development of which bones?
* What does bone arise from?
* Development of frontal, parietal, occipital and temporal bone (skull) as well as mandible and maxilla
* Bone arises from **primitive mesenchymal connective tissue** (NOT from cartilage)
* mesenchymal cells give rise to osteoblast
* bone formed within a "blastemal" lined by osteoblasts
61
Endochondral ossification is important for the development of which bones?
* Extremities
* Vertebral column
* Pelvis
62
* MOA of Endochondral ossification?
* Primary vs. Secondary ossification center?
* Chondroblasts lay down Type II collagen initially but t**hen Type X cartilage**
* _Primary ossification center:_
* form a periosteal collar of bone after apoptosis and calcification of matrix at the diaphysis
* _Secondary ossification center_
* forms at the epiphysis
*Vascularization* helps promote entrance of osteoprogenitor and hematopoietic cells
63
In bone what is happening in:
* zone of reserved cartilage
* zone of proliferation
* Zone of proliferation:
* reserve of chondrocytes
* Zone of proliferation:
* continuous cell division
* chondrocytes align as vertical and parallel columns
64
In bone, what is happening in:
* zone of hypertrophy
* zone of calcified cartilage
* zone of resorption
* _zone of hypertrophy_
* chondrocytes swell up with collagen
* are hypertrophic chondrocytes because of glycogen
* secrete more **Type X collagen** as well as **VEGF**
* _Zone of Calcified Cartilage:_
* __Chondrocytes become calcified
* promote **apoptosis** because diffusion of nutrients to cell is diminished
* _Zone of resorption:_
* __proliferation of osteogenic cells and vascular invasion
65
* Mechanism of fracture repair and bone healing?
* Begins with deposition of highly vascular collagenous granulation tisssue
* Chondroblasts develop to replace granulation tissue with hyaline cartilage
* provisional soft callus
* Osteoprogenitor cells from endosteum and periosteum go to work to create woven bone (hard)
* Woven bone gradually replaced with lamellar bone via remodeling
66
* Articular cartilage at the bony end plate has no?
* What is it separated from cartilage by?
* NO Haversion systems and canaliculi
* Separated from cartilage by a glycoprotein rich substance
* similar to cement lines
67
* What is the synoviam?
* What does it contain?
* **Outer layer of dense connective tissue (in joint capsule)**
* Inner synovial membrane with 1-2 layers of synovial cells
* NO basement membrane
* NO tight junctions
* Fenestrated capillaries
68
* Tendons are composed of?
* Where tendons insert into bones there is no?
* Composed of dense regular connective tissue
* regularly oreinted parallel bundels of collagen fibers separated by rows of fibroblasts
* NOTE:
* **ligaments secure bones and joints** but have a less orderly arrangement of collagen fibers
* Where tendon inserts into bone there is **no periosteum**
69
* Osteoid, the organic component of bone matrix is made of?
* Mostly **Type I collagen**
* **Osteopontin/ Osteocalcin**: only protein unique to bone
* produced by osteoblasts
* function in bone mineralization, Ca homeostasis
* **Cytokine and growth factors**
* control bone cell proliferation, maturation and metabolism
* **Glycosaminoglycans**
70
Osteoprogenitor cells are what kind of cells?
**Pluripotent mesenchymal stem cells** located at bone surface
71
* When do osteoblasts become osteocytes?
* What is function of osteocytes?
* Osteoblasts become osteocytes when they are _embedded_ within the matrix
* Osteocytes function to:
* communicate with each other and other bone cells via cytoplasmic process tunnels **(canaliculi)**
* control Ca and P levels in locally
* **Mechanotransduction**
72
How do osteoclasts perform bone resportion?
* _Bone resorption:_
* attach to matrix with cell surface integrins to create a sealed extracellular trench (**resorption pit)**
* secrete **proteases** into the pit to disolve matrix components
73
Osteoclasts differentiate by cytokines and growth factors, produced by osteoblasts, including?
* **M-CSF** (macrophage colony stimulating factor)
* IL-1
* TNF
74
* RANKL on osteoblast promote?
* OPG on osteoblast promote?
* **RANKL promote bone resorption**
* ****bind to RANK of osteoclast precursor and promote differentiation
* Enhanced by binding of M-CSF to receptor
* **OPG (Osteoprotegrin) promote bone formation**
* acts as _decoy_ receptor for RANKL
* inhibit osteoclast differentiation and resorption
75
Explain the process of paracrine cross talk between osteoblasts and osteoclasts?
* As bone is _resorbed_, factors are released (matrix proteins, GF, etc.) locally and stimulate osteoblast
* initiate bone renewal
* Osteoprogenitor cells produce **WNT** and **BMP**
* bind to receptors on osteoblasts and increase **production of OPG**
* promote bone formation
76
Senile osteoporosis is related to?
* Age related changes
* decreased proliferative and biosynthetic potential
* decrease response to GF
* _net result_: diminished capacity to make bone
77
Through what process does physical activity stimulate bone growth?
* Mechanical forces stimulate normal bone remodeling: **_Mechanotransduction_**
* strain/pressure of muscle contraction is transmitted to osteocytes through fluid in _canaliculi_
* mechanical signal stimulates secretion of factors that increase bone remodeling
* **stimulate osteoblast differentiation and activity**
* **decrease osteoclast activity**
* _result_: positive bone balance
78
How does a decrease in estrogen lead to postmenopausal osteoporosis?
* Decrease estrogen stimulates blood monocytes and bone marrow cells to secrete inflammatory cytokines
* **Increase RANKL and decrease OPG**
* increase osteoclast recruitment and activity
* decrease osteoclast apoptosis
* Resorption\>formation
79
MOA of Vitamin D hormone?
* Binds a nuclear receptor (vitamin D receptor, **_VDR_**) which associates with **RXR** to form a heterodimer
* Heterodimer binds to vitamin D response element (**_VDRE_**)
80
What is the result of Vitamin D deficiency?
* Impaired mineralization and accumulation of **unmineralized matrix**
* Can cause Rickets (children) and Osteomalacia (adults)
81
Compare Rickets and Osteomalacia to Osteoporosis
* _Osteoporosis_: mineral content is normal but **total bone mass is decreased**
* _Rickets_: decreased bone deposition in growth plate of developing bone
* _Osteomalacia:_ bone formed during remodeling is **undermineralized** resulting in predisposition to fractures
82
How can you differentiate between osteoporosis and osteomalacia?
* Abnormal blood levels of Vitamin D, calcium and phosphorus
* X-ray: slight cracks in bones
* **Looser transformation zones**; characteristic in osteomalacia
