mechanisms of bone. growth and deveopment Flashcards
what is bone
specialised CT
comprimossed of living cells embedded in mineralised eCM
bone types
trabecualr/cancellous/spongy
cortical/compact/laminar
woven
trabular/cancellous/spongy
inside
porous meshwork of bone
bone strengh determined by travecular microstructure
cortical/compact/laminar
dense
stronge
forms outerlate of bones
woven
forms during periods or repair or rapid growth
remodelled into lamellar bone
what lines the outer surface of cortical bone
periosteium
constituents of bone
30% organic
45% inoranic hydroxyapiite
hydroxyapitite consistant in
- 45% content bone
- 55% cementum
- 70% dentine
- 90% enamel
bone scaffold
- scaffold of interwoven collagen fibres
- Between the fibres are crystals of carbonated hydroxyapatite (small, plate like)
- Small amounts of non- collagenous proteins, some are unique to calcified tissue
eg osteocalciun, osteonectin, bone morphogenic proteins
bone functons
support
metabolic
endocrine
metabolic bone fucntion
haematopoiesis
calcium homeostasis
endocrine bone function
osteocalcin postive regultor of insulin secretion from pancrease
- osteocytes synthesize fibroblast growth factor 23 (FGF 23 has a role in phosphate homeostasis)
- Sclerostin, secreted by osteocytes inhibits bone formation
support bone function
supports body and protecs internal organs
allows moveent
periosteium
CT layer surrounding bone
where blood supply enters bone
contains nervous tissue
endosteum
inside layer
caniculi
link osteocytes to each other
cell types in bone
osteocyte osteoblast osteoclast bone lining cells osteoprogenetor cells
ostoeclast
resorb bone
large mutlinucleated
osteocyte
sense mechanical loads and Ca2+ homeostasis
bone lining cells
line periostela and endostela surfaces
osteoprogenitor cellls
precursors of osteoblastc linege
stem cells have partially differentiated towards osteoblasts
types of bone formation
intramembranous ossificaiton
endochonrdral ossification
Intramembranous ossificaiton
bone is formed direcly from condesned mesenchyme or ectomesenchyme
stem cells form osteoblasts directly
endochondral ossificaiton
cartilagenous precusor of the bone is formed and replaced by bone as it grows
(stem cells come together and from a cartilage precursor, chondrocytes
where does IMO occur
neurocranium
visercocranium
clavicle
intamembranous ossification steps
Mesenchymal stem cells condense, differentiate into osteoblasts and secrete extracellular matrix (osteoid) in long strands
- osteoblasts lay down bone mineral on the strands of osteoid (osteoid is the organic part of the ECM)
- slowly increase in size and length by laying down more bone on the outside of the little spinicles
- once the spinicles are mineralised and a little larger they are called trabeculae (don’t necessarily form trabeculae bone though)
- consecutive growth rings of osteoid (lamella) added onto the trabecula to increase thickness
- further bone growth by cycles of osteoid secretion and mineralisation (appositional growth – width growth)
- multiple trabecula within the developing bone contact one another to form a lattice structure
- areas of bones may completely fill in with mineralised osteoid (eventually ends up with cortical bone by remodelling)
- bones containing lattice structures are called primary trabecular bones
- most bones are mixtures of cortical bone outer surface and trabecular bone interior
endochonrdral ossification steps
ECO is three phase process
1) A miniature cartilage replica of a bone is formed by differentiation of mesenchymal or ectomesenchyme cells into chondroblasts which mature into chondrocytes
2) Cartilage grows in a specific direction – by interstitial (length) and appositional (width) growth
3) cartilage is converted into bone
- cartilage mineralisation draws in blood vessels which bring the stem cells in(mesenchymal cells)
- they then mature into the osteoblasts
- as the blood supplys it brings in the precursors of osteoclasts
- this leads to the remodelling, giving cortical bone on the outside and trabecular on the inside
- as the bone grows you get secondary ossification at the ends of the long bones
until the same process caries on, giving mature bone with bone marrow in the centre
growth plates, bone is situated where
- Epiphyseal bone at the top
- Metaphyseal bone underneath
mechanisms of ECO
- Chondrocytes are found in the reserve zone, quiescent
- when given appropriate signals the start to divide, giving proliferative zones
- they then get very big, and are called hypertrophic chondrocytes
- these cells undergo metabolic changes, start to resorb away some of the ECM
- deposit mineral on the cartilage surface
- release factors drawing in the blood supply
hypertrophic zone
- collagen X is being laid down so they can lay down the mineral on the matrix
- also produce factors such as vascular and endothelial growth factor, stimulates ingrowth of blood vessels
proliferation zone
parallel colums of dividing chondrocytes formation of the ECM
cartilage/bone interface
- Chondrocytes undergo apoptosis
- then get bone production in the mineralised matrix
(cartilage matrix mineralisation)
zones of epiphyseal growth plate in growing long bone
prolifertion zone
hypertrophic zone
cartilage/bone interface
remodelling occurs to
release calcium
alter architecture of cancellous one to meet new stresses or bone thats going to become cortical bone during bone growth so that it meets new stresses
phases of bone remodelling
1) Bone resorption phase
- bone ECM destroyed and removed
- This phase takes approx. 3 weeks
2) bone formation
- new ECM formed and mineralised
- 3-4 months
bone remodelling summary
1) bone resorption is initiated by recruitment of osteoclasts precursors (hemopoietic cells) to remodelling site
2) osteoclast precursors mature into osteoclasts by fusing together
3) bone lining cells erode a little ECM and leave the remodelling site
4) Osteoclasts bind to the ECM exposed by bone lining cells and digest the bone matrix with enzymes to form a resorption pit
5) osteoclasts release hydrochloric acid and also release proteinase (enzyme), which digests the organic phase away in the acidic environment, the acid dissolves the calcium phosphate
6) Calcium chloride is produced which is soluble and that can be removed into the ECM and flushed away by the interstitial fluids
7) Osteoclasts then stop digesting the matrix and die by apoptosis
8) osteoblast precursors recruited to the remodelling site
9) osteoblast precursors develop into mature osteoblasts
10) osteoblasts make new ECM to fill the resorption pit made by the osteoclasts
11) synthesis of matrix is complete the new bone surface becomes covered in bone lining cells
bone formation in socket after extacion
- Clot formation
- inflammatory cells which release chemokines
- new angiogenesis and the soft tissues
- migration and proliferation of those mesenchymal stem cells
- laying down of the new ECM
stem cells will then differentiate directly into osteoblasts, then start to lay down bone by IMO
bone formation in simple fracture time
6-8 weeks
Cleidocranial dysostosis
- rare genetic disorder that interferes with intramembranous ossification (skeletal dysplasia)
- Autosomal dominant defect in the RUNX2 gene (important in the differentiation of chondrocytes and osteoblasts
disorder of EMO
Achondroplasia
- recessive genetic condition affecting bone formation via ECO
