MSS: Cellular Stucture of Bone Flashcards
List some functions of bone.
- support and movement
- an attachment site for muscles (mechanical)
- protection for internal organs
- provides a home for bone marrow
- acts as a mineral reservoir (calcium)-metabolic
- collaborates with the endocrine system: is a source of some ‘non-classical hormones
What is the composition of bone?
It is 35% (ORGANIC)
- protein matrix
- bone cells (which contribute to the weight.)
65% (INORGANIC) minerals.
- calcium hydroxyapatite
- where 99% of calcium is found
- 85% of the Phosphorus
- 65% Sodium, Magnesium
Describe the organic (osteoid) protein matrix.
It is made up of mainly type 1 collagen.
It gives the bone both flexibility and tensile strength (the ability to resist stretching).
Describe the bone mineral.
It is mainly hydroxyapatite, which is hydrated calcium and phosphate (Ca10(PO4)6(OH)2).
It makes the bone rigid, brittle and gives it a high compressive strength (the ability to resist shortening).
(strength longitudinally)
What are the anatomical descriptions of the bones?
include functions
Anatomical bones
- Flat (protective function)
- long (limbs for large movements)
- short/cuboid (stability at joints, smaller and more precise movements)
- irregular (protect specific organs)
- sesamoid (pulley/reduce strain)
What are the macroscopic descriptions of the bone?
trabecular/cancellous/spongy bone (inner criss crosses)
cortical/compact bone (outer surface)
Cortical bone
- highly organised in repeating units called osteons, which are circular wrapped sheets of bone tissue (lamellae) organised around Haversian canals (which contain blood vessels, nerves etc)
- forms the outer surface of long and flat bones
- within the bone matrix (osteoid protein) there are lacunae cavities where osteocytes reside and are connected via minute canals called canaliculi
Trabecular Bone
- consists of the same structure as cortical bone, but with less organisation
- meshwork of bone tissue with spaces in between
- forms the inner surface of the bone
- within the bone matrix there are cavities called lacunae where osteocytes reside and are connected via minute canals called canaliculi
Compare the cortical and trabecular bone
CORTICAL long bones 80% of the skeleton appendicular skeleton 80-90% calcified mainly structural, mechanical, and protective
TRABECULAR vertebrae & pelvis 20% of the skeleton axial skeleton 15-25% calcified mainly metabolic large surface area
What are the microscopic descriptions of the bone?
- Woven bone (immature)
- Lamellar bone (mature)
Describe the structure of a long bone
What is the benefit of the growth plate?
compact bone (the outside)
spongy bone (the crisscrosses)
medullary cavity (space enclosed by cortical bone)
diaphysis (the main shaft in the middle)
epiphysis (shaft at the ends)
the growth plate/metaphysis (separates diaphysis and epiphysis)
Growth plate allows rapid linear growth
Define Endochondral ossification
Define Intramembranous ossification
Intramembranous ossification
- Direct differentiation of osteoblasts from connective tissue
- Flat bones
Endochondral ossification
- Bones form from a cartilage model
- Long bones
List the types of bone cells (and their origin).
The three main types of bone cells are:
- osteoblasts
- osteoclasts
- osteocytes
Mesenchymal (stromal) stem cells give rise to osteoblasts and osteocytes.
Haematopoietic stem cells give rise to all blood cells, and osteoclasts (which are the same lineage as macrophages).
Describe osteoblasts.
- bone-forming cells
- secrete osteoid to form new bone
- promote mineralisation of osteoid to become mature bone
- may terminally differentiate into osteocytes, found within the bone matrix (in lacunae)
- may remain inert along the bone surface and become lining cells
Describe osteoclasts.
- they are bone (digesting/) reabsorbing cells
- they are large and multinucleate which attach to the bone surface
- formed from the fusion of macrophages
- they secrete acid to dissolve bone minerals (releasing phosphate and calcium)
- they secrete enzymes (Cathepsin K- high affinity for type 1 collagen) to digest the organic matrix
- their life cycle is controlled by apoptosis
Describe osteocytes.
- they are terminally differentiated osteoblasts encased in the bone mineral matrix (lacunae)
- they extend multiple dendrites via minute canals in the bone matrix (canaliculi)
- the Lacunocanalicular system maintains communication between the bone surface and blood vessels
- they’re thought to coordinate osteoblast and osteoclast activity to achieve a balance between bone formation and bone reabsorption (BONE REMODELLING)
Describe bone remodelling in cortical bone.
Typically, there will be a leading edge where cells differentiate into osteoclasts and start digesting the bone. Behind that, there is osteoblast differentiation that will lay down new bone.
Thus, you have an advancing line of bone reabsorption and formation, which also leaves behind a ‘cement line’ that can be detected histologically.
Describe bone remodelling in trabecular bone.
Along the surface of the trabecular struts, there will be an osteoclast eating away at the bone, then osteoblasts subsequently forming new bone.
There are also lining cells on the surface of the bone that detach underneath this, forming a basic multicellular unit.
Describe the stages of bone remodelling.
- ACTIVATION: the promotion of differentiation of new osteoclasts
- REABSORPTION: the duration of osteoclast activity, removing bones and creating pits
- REVERSAL: the process by which you get osteoclast apoptosis, terminating its activity
- FORMATION: osteoblast differentiation; formation of new osteoblasts which line the bone surface, forming new osteoid (new bone which subsequently becomes mineralised)
What are some ways in which we can control bone remodelling?
Load-Bearing Exercise
-leads to micro-stress fractures detected by osteocytes which then coordinate a remodelling
Cytokines and other local signals
Endocrine Signals
- oestrogen inhibits osteocyte apoptosis and promotes osteoclast apoptosis, favouring bone formation over reabsorption
- androgens
Paracrine:
- RANKL
- Wnt signalling
What induces osteoclast differentiation?
RANK (receptor activator of nuclear factors kappa-B) ligand binding to RANK receptor on pre-osteoclasts, activating a transcription factor promoting differentiation of pre-osteoclasts into osteoclasts
What is RANK ligand expressed by?
osteoclasts, osteoblasts and pre-osteoblasts
What competes with the RANK receptor for the RANK ligand?
OPG (osteoprotogerin), a decoy receptor produced by osteocytes which prevents RANK-ligand from binding to RANK receptor, thus inhibiting osteoclast differentiation to prevent excessive bone reabsorption
Denosumab (monoclonal antibody)
RANK-ligand inhibitor, preventing RANK receptor activation and inhibiting osteoclast differentiation, thus inhibiting the reabsorption phase of the bone remodelling cycle
What is denosumab used for?
- osteoporosis (loss of bone density)
- inhibits osteoclast differentiation
- inhibits further bone reabsorption
- mimics osteoprotegerin (OPG)
How are osteoblasts differentiated?
via the Wnt Signalling Pathway:
1) Wnt is a signalling protein molecule that will activate the Wnt receptor (frizzled) in presence of co-factor LRP5
2) ß-catenin protein in the cytosol is then released allowing it to act as a transcription factor and promoting specific differentiation pathways (osteoblast differentiation)
Negative Regulation of Wnt Signalling Pathway
DKK (dickkopf) and sclerostin (SOST) proteins bind LRP5 co-receptor and prevent full activation of Wnt signalling pathway, preventing osteoblast differentiation
Osteoporosis (common bone disease)
loss of organic bone mineral density (normal part of ageing), resulting in brittle bones making you more prone to fractures
Osteomalacia (less rare)
loss of the bone mineral component/failure of mineralisation of the osteoid, resulting in the softening of the bones
Osteoporosis Pseudoglioma
Co-receptor LRP5 gene mutation in the Wnt signalling pathway, affecting key signals:
- no osteoblast differentiation
- very poor bone development
- very fracture prone
- early blindness due to failure and abnormalities of retinal development
Sclerosteosis and Van Buchem Disease
SOST gene mutation:
- inactivated sclerostin protein of the Wnt signalling pathway
- overaction of Wnt signalling pathway
- increased osteoblast differentiation causing excess bone formation
- high bone mineral density above average
What happens during osteoporosis?
Mutation inactivates RANK-ligand protein:
- prevents osteoclast differentiation
- preventing bone reabsorption
- bone more rigid and brittle
Bone density loss with age
peak bone density achieved at 25-30, and thereafter it is a slow downhill process, somewhat accelerated in women due to the fall in oestrogen levels post-menopause
