Body structure bone Flashcards
haematopoeis
formation of blood cellular compounds
understand bone structure/matrix
cortical/compact bone
* sits outside/round bone
* 80% of total bone mass
* protects and provides strength to structure
* 10% porous
trabecular(cancellous) bone
* highly porous 50-90%
* network of trabeculae in directions of stress
* 20% of total bone mass
* Provides a large bone surface for mineral exchange – 4X more active than cortical bone
* Helps to maintain skeletal strength and integrity.
Bone Marrow
Found within bones, either red or yellow marrow.
(Red marrow produces blood cells, while yellow marrow stores fat.)
nanostructures of different bone structures
made of densely packed collagen fibrils
there are different kinds of collagen and this one is type 1 collagen
aligned parallel to provide the dense extracellular matrix and capacity to withstand load
components of ECM
ECM = extracellular matrix
consists of collagen and hydroxyapatite
collagen provides elasticity and that dense ECM.
–> collagen are cross linked together to form the parallel alignment, densely packed.
–> cross links that glue the collagen fibres together.
Collagen without the mineral component = bendy bones.
Mineral component –> hydroxyappetite crystals that are formed embed themselves in within the spaces that are left between the collagen fibres.
Cells that make bone lay down collagen and mineralise it with these hydroxy appetite crystals.
Hydroxyapatite has multiple little calcium ions that are part of its structure,
–> provide some rigidity to this
–> bones need to be hard, strong (hydroxyapatite) and flexible (collagen)
balance between collagen and hydroxyapatite
1) when there is little collagen, too much hydroxyapatite = bones are brittle, likely to snap and don’t give and bend, hypermineralised
–> the collagen is not aligned correctly for the bones to bend and be flexible, cannot respond and load
2) when there is too much collagen and little hydroxyapatite = bones are too bendy!
Bone Modelling and Remodelling
Why does bone matrix need to be turned over?
- Obtain optimal shape in response to load (can change shape to adapt to load)
- replace and epair damage to skeleton (fracture and microcracks to prevent strains on bone)
- Prevent accumulation of aged tissue/micro- damage
- Supply calcium and phosphorous for mineral homeostasis for organ function (PNS and Muscle)
The nerves can’t signal with no calcium present –> muscles cannot contract
therefore = skeleton provides a reservoir through bone remodelling
bone cells
osteocytes sitting in the bone matrix
osteclasts, the bone resorbing cells
osteoblasts = the bone forming cells
–> these 3 cells that perform and coordinate constant turnover and remodelling of cells
bone remodeling/turnover
1) Quiescent
osteocytes sitting in the bone and
these bone lining cells just sitting across the bone surface= not active.
2) Activation
Stimulus: Mechanical stress, micro-damage, hormonal changes, or metabolic signals trigger the need for bone remodeling
Signaling: Osteocytes, embedded in bone, sense the signals and initiate the remodeling process.
precursor cells for osteoclasts are recruited to the site
3) Resorption
they fuse to form osteoclasts and these red multi nucleated cells here eat away at the bone.
They eat a big hole in the bone where it
needs to be removed.
Osteoclasts break down old bone tissue by secreting acids and enzymes, releasing minerals (such as calcium and phosphate) into the bloodstream. Then, osteoclasts undergo apoptosis and the resorption site is prepared for new bone formation.
4) Formation
Osteoblasts are recruited to the resorption site
Osteoblasts lay down new bone matrix, including collagen fibers and minerals (hydroxyapatite).
5) Mineralisation
Osteocytes: Some osteoblasts become embedded in the newly formed bone matrix and differentiate into osteocytes.
Maturation: The new bone undergoes maturation, achieving its final structure and strength.
Calcification: Mineralization occurs as calcium and phosphate ions precipitate on the collagen matrix.
6) Quiescent Phase:
Resting Period: After formation, bone can enter a quiescent phase where there is no active remodeling.
Maintenance: Bone remains in this phase until new signals or stresses trigger the need for further remodeling.
osteoblasts
Derived from mesenchymal lineage (type of stem cells that can differentiate for different functions including bone formation)
* Can terminally differentiate into an osteocyte or return to resting bone lining cell
* P1NP collagen fiber component (cleavage product used as serum marker for bone formation) cleaved during matrix formation
* Forms organic matrix, osteoid, and then
mineralizes it [2 step process]
1) form organic matrix = osteoid (collagen matrix)
- produce procollagen which is the precursor to collagen
- cells cleave or cut the ends off the procollagen molecule “tidying it up” = the formation of mature and functional collagen fibers as well as cleavage products [markers]
- collagen type 1 (Col1) particles then align, and cross link
- crosslinking to increase strength and stablility
2) mineralisation
- deposit minerals such as calcium and phosphate onto organic matter
- gives structural integrity
P1NP
- Procollagen Type 1 N-Terminal Propeptide
- one of the cleavage products during bone formation
- secreted by osteoblasts and goes into the blood.
- serum levels of P1NP can tell us how much bone patients are forming and how active their osteoblasts are.
One of the serum markers that we use
very commonly in the clinic.
serum markers and serum levels
A serum marker is a substance or molecule that can be measured in the liquid portion of blood, known as serum.
“Serum levels” specifically refer to the concentration or amount of a particular substance present in the blood serum.
osteoclasts
Osteoclasts are bone-absorbing cells derived from hematopoietic precursor cells.
multinucleated cells [not common in many cells in the body] formed by the fusion of precursor cells.
–> primary role is to resorb the bone matrix, REVERSE of bone formation
bone resorption
1) first adhere to a specific area on the bone surface, creating a sealing zone.
2) They secrete acid into this sealing zone, leading to demineralization of the bone matrix by breaking down hydroxyapatite (mineral component).
3) Proteases are produced by osteoclasts to break down the collagen matrix, an organic component of bone.
4) As a result of this process, calcium is liberated from the bone and released into the circulation.
CTX, NTX and PYR/DPD are released during cleavage
used as serum markers to see how active osteoclasts are breaking down bone matrix
CTX = secreted in blood to measure bone resorption.
osteocytes
Osteocytes are embedded within the bone matrix
* are terminally differentiated osteoblasts.
* form a network of connections with each other, creating a canalicular network within the bone matrix [since osteocytes are master regulators of bone formation is uses this network to communicate]
* release factors : (RANKL = major regulator of bone resorption) and (OPG = ) osteoclast formation and activity
* Release factors which decrease (Sclerostin) osteoblast activity = ensure theres not too much bone
canalicular network
-> network allows osteocytes to communicate with each other,exchange of information.
also use network to sense and respond to mechanical forces and loads applied to the bone.
When the bone is subjected to forces, there is a shift in fluid flow through the canalicular network.
Osteocytes sense this fluid flow change and respond to alterations in load, providing a mechanism for the bone to adapt to different pressures.
RANKL
rank ligand
released by osteocytes and binds to the receptor on osteoclasts precursors
–> leads to downstream formation
of osteoclasts.
So if your osteocytes decide there’s micro damage etc, RANKL levels will go increase.
