Cellular structure of bone Flashcards
What are the functions of the bone?
- Support and Movement: attachment site for muscles
- Protection for internal organs
- Provides home for bone marrow
- Mineral Reservoir (e.g. serum calcium)
- Endocrine Function: source of some ‘non-classical hormones’
What are the types of bone structure?
Cortical (compact) bone
Trabecular (spongy, cancellous) bone
What us the cortical bone?
- highly organised in repeating units called osteons, which are circular wrapped sheets of bone tissue (lamellae) organised around little central canals called Haversian canals (which contain blood vessels, nerves etc)
- forms outer surface of long and flat bones
- within the bone matrix (osteoid protein) there are cavities called lacunae where osteocytes reside, and are connected via minute canals called canaliculi
What is the Trabecular Bone?
- consists of the same structure as cortical bone, but with less organisation
- meshwork of bone tissue with spaces in between
- forms inner surface of bone
- within the bone matrix (osteoid protein) there are cavities called lacunae where osteocytes reside, and are connected via minute canals called canaliculi
What is the Composition of cortical and trabecular bone?
Same composition and cell types:
- protein: organic osteoid matrix (25%)
- mineral: 75% (hydroxyapatite- calcium and phosphate)
- cells
What is the organic component of bone?
The osteoid matrix (mainly collagen)
What gives bone its strength?
Organic osteoid matrix (mainly type 1 collagen) and mineral component (mainly calcium and phosphate) are mixed together to give bone its strength
Type 1 Collagen in Organic Osteoid gives bone…
Flexibility and tensile strength
Hydroxyapatite makes bone…
brittle and rigid, giving high compressive strength (strength longitudinally)
What are the major classes of bone cells?
3 major classes:
- Osteoblasts
- Osteoclasts
- Osteocytes
Also, bone marrow cells:
- mesenchymal (stromal) stem cells
- haematopoietic stem cells
What are the Bone forming cells?
Osteoblasts:
>forms organic osteoid matrix & promote its mineralisation
may terminally differentiate into osteocytes, found within the bone matrix (in lacunae)
may remain inert along the bone surface and become lining cells
What are osteoblasts derived from?
Mesenchymal (stromal) stem cells
What are the Bone reabsorbing cells?
Osteoclasts:
>large multinucleated cells which attach to bone surface and secrete:
-acid to dissolve bone mineral (releasing phosphate and calcium)
-enzymes (Cathepsin K- high affinity for type 1 collagen) to digest organic matrix
> life cycle controlled by apoptosis
What are osteoclasts derived from?
Haematopoietic stem cells
What are Osteocytes?
terminally differentiated osteoblasts encased in lacunae
extend multiple dendrites via minute canals in bone matrix (canaliculi) which connect lacunae to each other and to bone surface, where they will be in contact with blood vessels (lacunocanalicular system)
What is the role of the Lacunocanalicular system in osteocytes?
maintains communication with bone surface and blood
What is the Osteocyte activity?
thought to coordinate osteoblast and osteoclast activity to achieve a balance between bone formation and bone reabsorption (BONE REMODELLING)
Describe Bone remodelling.
osteoclasts dissolve old bone and osteoblasts replace it with new bone in a continuous process of bone recycling
osteoclasts will differentiate in response to appropriate signals and then undergo apoptosis in response to other signals
What are the Stages of Bone Remodelling?
1) Activation
- stimulation of osteoclast differentiation
2) Reabsorption
- governed by the lifecycle of the osteoclast
3) Reversal
- signals to terminate osteoclast activity (osteoclast apoptosis) and promote further osteoblast differentiation
4) Formation
- osteoid mineralisation and new bone formation
Describe how bone remodelling is controlled.
Load-Bearing Exercise
-leads to micro-stress fractures detected by osteocytes which then coordinate remodelling
Cytokines and other local signals
Endocrine Signals
- oestrogen inhibits osteocyte apoptosis and promotes osteoclast apoptosis, favouring bone formation over reabsorption
- androgens
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
What is Denosumab (monoclonal antibody)?
RANK-ligand inhibitor, preventing RANK receptor activation and inhibiting osteoclast differentiation, thus inhibiting the reabsorption phase of the bone remodelling cycle
