Bone and Cartilage Flashcards
functions of cartilage
1) support and framework
2) shock absorption, resisting compression
3) smooth gliding surfaces
what is the most abundant cartilage
hyaline
chondrocyte
cells responsible for synthesis of cartilage-specific ECM components
chondroblasts
chondrocyte precursors capable of forming cartilage-specific ECM but not encased in matrix
lacunae
spaces where cells are living/ existing in
abundant organelles in chondrocyte structure
lots of RER, prominent golgi - proteoglycans
what cells do chondrocytes originate from
mesenchymal stem cells
transcription factor required for expression of cartilage-specific ECM
Sox9
what happens if there is a lack of Sox9
prevents mesenchymal progenitor cells from differentiating to chondrogenic cells
what is cartilage ECM made of
ground substance with proteoglycan aggregates and glycosaminoglycans (GAGs) that are negatively charged side chains
special characteristics of cartilage
-avascular
-nutrients and oxygen diffuse through the ECM
- limited growth and repair
because oxygen is limited in cartilage, chondrocytes have _______
a low metabolic rate, and dont require high oxygen concentrations to perform normally
perichondrium
-dense CT surrounding cartilage
-contains vasculature, nerves and lymphatic vessels
-outer layer has fibroblasts
-inner layer has chondroblast precursors
2 types of growth in cartilage
appositional and interstitial
appositional growth
differentiation of chondrocytes from pericardium
interstitial growth
results from mitotic division of pre-existing chondrocytes within matrix (growth from within)
location of hyaline cartilage
-articular surfaces of moveable joints
-walls of respiratory passages (nose, larynx, trachea, bronchi)
-costal cartilage (ribs)
-epiphyseal growth plates
types of fibers in hyaline cartilage
type II collage
what kind of growth occurs in hyaline cartilage
appositional and interstitial
articular cartilage
type of hyaline cartilage,
-covers articular surfaces of bones
-lacks perichondrium
-gets nutrients and oxygen from synovial fluid (diffusion)
elastic cartilage
similar to hyaline, but has large network of elastic fibers
locations of elastic cartilage
ear, auditory canals, Eustachian tubes, epiglottis
fibers in elastic cartilage
type II collagen and elastic fibers
what kind of growth occurs in elastic fibers
appositional and interstitial
Fibrocartilage
tissue intermediate between Dense CT and hyaline cartilage
no distinct perichondrium
locations of fibrocartilage
intervertebral discs, attachments of certain ligaments, pubic symphysis and menisci
fibers in fibrocartilage
type I collagen, small amounts of type II collage
what type of growth in fibrocartilage
interstitial
bone
largest proportion of body’s connective tissue mass
functions of bone
-framework
-levers for locomotor function
-protect vulnerable viscera
-site for hematopoiesis (bone marrow)
-maintain mineral (calcium) homeostasis
2 layers in bone
compact (cortical) and spongy (trabecular)
3 distinct areas on a bone
epiphysis, metaphysis and diaphysis
components inside the diaphysis
-medullary cavity filled with bone marrow
-endosteum- contains osteoprogenitor cells
-periosteum- membrane around bone
bone ECM composition
65% calcium hydroxyapatite, 23% collage, 10% water, rest non-collagen proteins
what cells make up cortical bone
osteons
osteoblasts
responsible for the synthesis and mineralization of bone ECM
-can be cuboidal and sometimes columnar
bone-lining cells
osteoblasts that became quiescent
where do osteoblasts originate from
mesenchymal stem cells
what transcription factor is required for the expression of bone-specific ECM from mesenchymal cells
Runx2
lack of Runx2/Cbfa1 results in what
lack of osteoblasts, hypertrophic chondrocytes, and a skeleton without any mineralized matrix
osteocytes
terminally differentiated osteoblasts that are encased in ECM, contact other osteocytes with dendritic processes, live in lacunae
osteoclasts
opposite of osteoblasts, responsible for bone resorption or degrading mineralized bone
-large mutinucleated cells
where are osteoclasts derived from
hematopoietic stem cells, share a common progenitor with monocyte/macrophage
characteristics of osteoclasts
large, multi nucleated, polarized, clear zone and ruffled border
has mitochondria for energy, ion pumps to keep pH acidic,
what breaks down bone in a osteocyte
lysosomal enzyme cathepsin K
how do bone cells regulate their functions
they balance bone formation and resorption to maintain structural integrity, communicate with one another
macrophage colony stimulating factor (M-CSF)
stimulates early commitment to osteoclast lineage
receptor activator of NF-kB (RANK) and its ligand (RANK-L)
induces osteoclast formation and activation
osteoprotegerin (OPG)
produced by osteoblasts, acts as a RANK-L decoy receptor
the ratio of RANK-L/OPG is _____________ to the number of osteoclasts
directly proportional
trabeculae provide a _____________ for rapid deposition and release of calcium
large surface area
PTH
gets released in response to low calcium levels, stimulates osteoclasts
what happens when PTH is released
-osteoclastic bone resorption
-renal calcium reabsorption
-activated vitamin D stimulate bone resorption
what is important for maintaining bone mass
mechanical forces, load-bearing activities, staying active
-slows down bone loss and increases deposition of minerals/ production of collagen fibers
osteoperosis
what factors contribute to osteoporosis
-aging
-post-menopausal
-disuse
-inflammation/arthritis
-diabetes
what happens to RANKL/OPG ratio in osteoporosis
its increased
osteopetrosis
autosomal recessive, caused by gene mutations that affect osteoclast development and function
-decreased bone resorption
symptoms of osteopetrosis
-increased fractures
-cranial nerve defects
-anemia and infections
treatment of osteopetrosis
bone marrow transplant
Rickets/Osteomalacia
rickets in kids, osteomalacia in adults
-defective Vitamin D intake or metabolism
-defective mineralization of osteoid
-increased osteoid thickness
-increased fracture risk
rickets/osteomalacia treatment
Vitamine D supplementation
rickets in lower limbs
cause bowing
cleidocranial dysplasia (CCD)
autosomal dominant skeletal dysplasia, caused by mutation in Runx2 gene on chromosome 6
characteristics of CCD
-no clavicles
-delayed closure of cranial sutures
-short
-scoliosis
-teeth abnormalities
Fibrodysplasia Ossificans Progressive (FOP)
rare autosomal dominant genetic disorder of ectopic bone formation
-mutated ACVR1 gene responsible for encoding BMP type 1 receptor
-cause progressive endochondral ossification of muscle, tendons and ligaments
FOP symptoms
bone forms where it shouldn’t, excessive bones in joints and muscles
osteogenesis imperfecta
brittle bone disease, genetic disorder, fragile bones break easily
-dominant mutation in type I collagen genes
osteogenesis imperfecta over time
-acute = few fractures and normal life expectancy
-chronic = many fractures and shortened life expectancy
-no cure
two processes in osteogenesis
intramembranous and endochondral
intramembranous osteogenesis
bone tissue is formed directly in primitive connective tissue (mesenchyme)
-skull
endochondral osteogenesis
bone tissue replaces a hyaline cartilage template
-most bone in body
steps in intramembranous bone formation
-mesenchymal cells condensate
-differentiate to osteocytes and form bone matrix
-calcium is deposited from blood vessels to mineralize osteoid
endochondral bone formation
-hyaline cartilage develops
-cartilage calcifies, periosteal collar forms around diaphysis
-primary ossification center forms
-secondary ossification center forms in epiphyses
-bone replaces cartilage, except articular
-epiphyseal plates ossify and form epiphyseal lines
4 zones of endochondral bone formation
resting, proliferating, hypertrophic, ossification
how is the length of cartilage increases during proliferating zone
chondrocytes run away from osssification
where does calcification of cartilage matrix surround
hypertrophic chondrocytes
how does bone increase in outer circumference
periosteal bone formation
what increases the inner bone circumference
endosteal bone resorption,
can also increase size of bone marrow cavity
how does the thickness of the cortical bone gradually increase over time
net periosteal formation exceeds net endosteal resorption
indian hedgehog (Ihh)
protein produced by pre-hypertrophic and early hypertrophic chondrocytes
function of ihh
-stimulates synthesis and secretion of PTH-RP
-regulates formation of periosteal bone collar
PTH-RP
function of PTH-RP
-stimulates chondrocyte proliferation
-prevents them from differentiating into hypertrophic chondrocytes
what do hypertrophic chondrocytes secrete
type X collagen
what is type X collagen
a marker of terminal differentiation and vascular endothelial growth factor (VEGF)
what is VEGF
an inducer of vascular invasion
what does the site of a fracture tell you
it determines the healing process of the fractured bone
3 general steps of fracture healing
1) hematoma formation
2) callus formation
3) bone remodeling
hematoma formation
- pain, warmth
-recruitment of MSC progenitor populations - low pO2 at fracture site so chondrocytes produce cartilage
callus formation
soft callus: development of fibrous and cartilaginous collar to surround fracture
-callus widens and immobilizes fracture ends
hard callus: initial bone formation
-endochondral ossification of cartilage, intramembranous on bone surface
bone remodeling
conversion of immature to mature bone
-haversian system reconstituted
-more bone is deposited in areas of greater stress
factors that influence the rate of fracture healing
size of gap, age, blood supply, Ca2+, phosphate, nutrition
joint
region where bones join together
2 types of joint
diarthroses and synarthoses
diarthroses
permit free bone movement
synarthroses
permit limited or no movement
types of synarthroses
synotosis, synchrondrosis, syndesmosis
synotosis
bones united by bone tissue, no movement
-cranial sutures
synchondrosis
bones united by hyaline cartilage with limited movement
-epiphyseal plates, costal cartilages connecting ribs to sternum
syndesmosis
bones joined by dense CT or fibrocartilage with limited movement
-pubic symphysis and intervertebral discs
