Describe cartilage.
hyaline cartilage - type II collagen
elastic cartilage - hyaline and elastic fibers
fibrocartilage - type I collagen
composed of chondrocytes and extracellular matrix (ECM)
Describe the composition of cartilage.
intracellular water - 60-80%
cells - chondroblasts and chondrocytes (3-5%)
- chondroblasts become chondrocyte when surrounded by cartilage
collagen - predominately type II (15%)
- specialized ECM (95 of cartilage), with major type is II (80%)
proteoglycan
Describe the components of hyaline cartilage.
collagen:
- major matrix protein
- type II - provides tensile strength, shape, and resists osmotic swelling from aggrecan
hyaluronan:
- linear polymer that intertwines when type II collagen and binds proteoglycan (made up of GAGs)
aggrecan - the proteogly
Where can hyaline cartilage be found?
fetal skeletal tissues
epiphyseal plates
articular surface of synovial joints
costal cartilages of rib cage
cartilages of nasal cavity, larynx, and rings of trachea
plates of bronchi
What are the functions of hyaline cartilage?
resists compression
provides cushioning
smooth and low friction surface for joints
structural support in respiratory system
foundation or development of skeleton
Describe growth of hyaline cartilage.
Perichondrium is derived from mesenchyme so there are some mesenchymal cells in this layer. There are two methods of growth - interstitial and appositional
perichondrium layer -> layer of appositional growth
-> layer of interstitial growth
Describe the interstitial growth of hyaline cartilage.
- mitosis of chondrocytes
- mitosis of chondrocytes gives rise to new chondrocytes which secrete ECM expanding the cartilage
Describe the appositional growth of hyaline cartilage.
- formation of new chondroblasts (inner cell layer of perichondrium) express SOX-9 (transcription factor).
appositional growth:
cells in perichondrium (inner cell layer begin expressing TF Sox-9 -> chondroblasts -> secrete ECM
when completely surrounded b
Describe the perichondrium of hyaline cartilage.
- connective tissue lining of hyaline cartilage composed of dense irregular connective tissue
two layers - outer and inner
- outer fibrous layer: look at the nuclei, they are flat/squamous shaped
- inner cellular layer: again look at the nuclei, they are
Describe chondrocytes.
- produce all of the components of ECM and then help maintain it.
- can be present as a single cell or an isogenous group.
- chondroblasts can divide and give rise to chondrocytes once surrounded by ECM, however the chondroblasts -> chondrocytes and divis
Describe an isogenous group
forms when a single chondrocyte divides, giving rise to two chondrocytes, but the ECM prevents the cells from moving too far from each other, so they form groups
Describe the composition of chondrocytes.
- store lipid and glycogen
- sit in a depression called a lacunae
- surrounded by a capsular matrix (more basophilic) that contains lots of sulfated groups
- a territorial matrix surrounds the entire isogenous group, containing type II collagen and less s
In what situations does the ossification of hyaline cartilage occur?
1. calcification of articular cartilage occurs where it contacts bone
2. Endochondrial ossification (replacement of hyaline cartilage by bone as a normal fetal development)
3. Aging induced calcification
Describe damage to cartilage.
- can tolerate intense/repetitive stress
- when damaged, it has a limited ability to repair itself because it is avascular, chondrocytes are embedded in matrix and thus have limited mobility ability to divide.
Describe repair of hyaline cartilage involving the perichondrium.
- limited repair can occur if the perichondrium is involved in the damage
- progenitor cells from the perichondrium can become chondroblasts and begin secreting ECM, forming mostly scar tissue (type I collagen).
Describe the repair of hyaline cartilage in adults.
- angiogenesis at the site of the wound is common
- new blood vessels bring in calcium, which calcifies the hyaline cartilage, forming new bone.
- frequently causes complication in open heart surgery where the costal cartilage is cut to gain access to the
Describe calcification.
- always occurs in cartilage that is about to be replaced by bone (endochondrial ossification) during an individual's growth period.
- hyaline cartilage in adults calcifies with time as a part of the aging process.
- in most situation, cartilage that calc
Describe articular cartilage.
- consists of hyaline cartilage
- lacks a perichondrium
- 4 zones - superificial, intermediate, deep, and calcified
- mature articular cartilage has a very slow growth rate
Describe the different zones of articular cartilage.
- superficial (tangential) zone - pressure resistant and closest to articular surface
- intermediate zone
- deep (radial) zone - chondrocytes arranged in short columns perpendicular to free surface of cartilage and collagen. its fibers are parallel to lon
Describe a joint injury.
results in calcification of subchondrial bone which increase thickness of subchondrial bone plate.
Describe elastic cartilage.
- no age-induced calcification
- hyaline cartilage that has branching and anastomosing elastic fibers
- visualized best with special stains
- provides resilience, pliability, and elastic properties
- contains isogenous groups with chondrocytes
- surrounde
What the locations of elastic cartilage?
- pinnae of external ear
- walls of external acoustic meatus
- auditory (Eustachian) tube
- epiglottis
What are the locations of fibrocartilage?
- intervertebral discs (IVDs) - equal types
- pubic symphysis
- articular disc of sternoclavicular joint
- articular disc of temporomandibular joint
- menisci of knee joint - more type 1
- triangular fibrocartilage complex of the wrist
- site of tendon at
Describe fibrocartilage.
- resists both compression and shearing forces, acting as a shock absorber.
- the ratio of type 1:type 2 collagen varies with site and age - type 2 increases with age.
- consists of chondrocytes (round nuclei) and their matrix (type II collagen) and dense
Describe bone.
- specialized connective tissue with a mineralized matrix
- mineral used to form bone is calcium phosphate which from hydroxyapatite crystals
- storage for calcium and posphate
What are the functions of bone?
- support and protection
- storage of calcium and phosphate
- homeostatic regulation of blood calcium levels
What are the different types of bone tissue?
compact:
- dense, outer layer
spongy:
- meshwork space within
- filled with marrow and blood vessels
- interior of bone
Describe the bone matrix.
- type 1 collagen (90%) and ground substance (10%) which are both mineralized to form bone
- contains proteoglycans, adhesion glycoproteins, vitamin K dependent proteins, growth factors, and cytokines.
Describe the proteoglycans of the bone matrix.
- especially osteoadherin which is used to specific bone and binds to the hydroxyapatite crystals
- help with compressive strength and binds growth factors
Describe the adhesion glycoproteins of bone matrix.
- especially osteonectin
- acts as a glue between collagen and hydroxyapaptite crystals
Describe the vitamin K dependent proteins of the bone matrix.
- specific to bone
- osteocalcin binds calcium from blood and stimulates osteoclasts during bone remodeling
Describe the growth factors and cytokines of bone matrix
- many different kinds
- BMP7 aka osteogenic protein 1 (OP1) is used clinically to induce bone growth post bone surgery
- induce differentiation of mesenchymal cells, creating osteoblasts
Describe long bones.
- periosteum cover bone except at site of articulation, where articular cartilage is found
- two layers
- endosteum lines bone cavities
- contains both red and yellow bone marrow
- epiphyses are mostly spongy bone
- diaphysis is all compact bone
Describe the different types of bone marrow found in long bones.
red bone marrow - site of blood cell development
yellow bone marrow - age-dependent replacement of red bone marrow with adipocytes, but has the ability to turn back into red marrow.
Give the difference between the periosteum and the endosteum.
- The outer surface of the bone is the periosteum and dense irregular tissue
- The inner surface of the bone is the endosteum
- Bone appearance is VERY acidophilic with H&E - osterocytes look like pepper on mashed beets
Describe immature bone
- woven bone
- non-lamellar bone
- more cells that have a random arrangement
- absence of lamellar appearance
Describe the differences between mature compact bone and mature spongy bone.
mature compact bone has a lamellar appearance
mature spongy bone has a trabecular network
Describe the structure of mature bone.
- structural unit is the osteon, or Haversian system, which is arranged in concentric lamellae of osteocytes that surround the Haversian canal.
- blood vessels and nerves travel through the Haversian canal will branch at right angles into Volkmann canals
Describe what happens as bone matures.
- undergoes remodeling which will destroy the normal architecture of the osteon, resulting in interstitial lamellae
- contains an outer circumferential lamellae covered by the periosteum and an inner circumferential lamellae covered by the endosteum
- col
Describe the cells of bone.
- bone lining cells - two types - osteoblasts and osteoclasts. osteoblasts make bone while osteoclasts resorb bone.
- mesenchymal stem cells present in the periosteum or brought in by the blood vasculature system via Haversian canals -> osteoprogenitor ce
What are the clinical markers of osteoblast activity?
plasma levels of tissue non-specific alkaline phosphatase (TNAP) and osteocalcin.
Describe osteoblasts
- sit on surface of the bone (bone-lining cell)
- appearance can vary with shape from squamous (inactive) to columnar (active).
- single layer with a single nucleus
- secretes type I collagen and osteoid (bone matrix proteins)
- have receptors for PTH ->
Describe the osteoid components of osteoblasts.
- calcium-binding proteins like osteocalcin and osteonectin
- adhesion proteins like osteopontin
- proteoglycans
- tissue non-specific alkaline phosphate (TNAP)
- less mineral content, so it will stain paler than bone matrix
Describe osteoclasts
- bone resorption
- Howship lacuna
- large, multinucleated cell
What is an important clinical marker for osteoclasts activity and differentiation?
tartate-resistant acid phosphatase (TRAP).
Describe osteoclast differentiation/maturation.
1. Precursor cells express RANK (receptor for activated nuclear kappa b)
2. Stromal cells and/or T cells secrete or RANK ligand which causes precursor cells to differentiate and mature into osteoclasts
3. Osteoblasts secrete OPG (osteoprotegerin), which a
Describe activated osteoclasts.
- polarized
- ruffled border that increases surface area for exocytosis of hydrolytic enzymes and proton secretion
- hydroxyapatite crystal between processes of ruffled border
- clear zone located next to the ruffled border, marks the limits of bone resop
Describe bone resorption.
1. decalcification of bone matrix via acidification -> starts digestion of matrix: carbonic anhydrase -> carbonic acid -> HCO3 and H+ -> pH of 4-5 in ruffled border -> digestion of bone mineral hydroxyapatite -> produces calcium, phosphate, and water
2. e
Describe the regulation of osteoclast activity.
1. PTH, secreted by the chief cells of the parathyroid, indirectly regulates osteoclasts
2. T cells, osteoblasts, and osteocytes have receptors of PTH.
3. In response to prolonged exposure to PTH, T cells increase secretion of soluble RANK ligand. Osteobl
What are the different types of bone formation?
- also called ossification
- endochondrial - uses hyaline cartialge
- intramembranous - no hyaline cartilage (flat bones of skull, face, and clavicle)
Describe intermembranous ossification.
1. ossification center appears in mesenchymal connective tissue containing osteoprogenitor cells -> osteoblasts -> secrete unmineralized matrix (osteoid)
2. trapped osteoblasts -> osteocytes as mineralization occurs
3. immature, woven bone -> spongy and c
Describe endochondrial ossification.
- mesenchymal cells -> type II collagen -> chondroblasts -> cartilage matrix -> hyaline cartilage model formed -> grows by interstitial (length) and appositional (width) growth
- osteoblast formed -> bony collar at diaphysis
- chondrocytes in mid-region o
Describe the different epiphyseal plate zones.
diaphysis -> epiphysis
zone of resorption -> zone of calcified cartilage -> zone of hypertrophy -> zone of proliferation -> zone of reserved cartilage
What are the four events that occur during endochondrial bone formation?
1. hypertrophy
2. calcification
3. chondrocyte death
4. osteoid on cartilage
Describe the mineralization of bone.
1. Osteoblast secrete osteocalcin which binds calcium -> increasing local calcium concentration -> secretion of TNAP -> increases local phosphate concentration -> increases calcium
2. Osteoblasts secrete matrix vesicles -> binds type I collagen
3. Initial
What is the primary ossification center?
where bone begins to form in the diaphysis of a long bone
What is a mixed spicule?
combination of bone and the underlying calcified cartilage
What can act as a clinical determination of various bone disorders?
plasma levels of OPG and RANK ligand
What is the underlying cause of osteoporosis?
prolonged exposure to PTH causes the osteoclasts to become hyperactive