Cellular structure of the bone Flashcards
What are the 5 functions of the bone?
- Support and movement: attachment site for muscles
- Protection for internal organs
- Provides home for bone marrow – blood and stems cells
- Acts as mineral reservoir – calcium and phosphate. Need in various physiological functions
- Endocrine: source of some ‘non-classical’ hormones
Describe the structure of the bone
- The outer layer is made of cortical bone (compact bone) which has a regular repeating structure called ostions.
- Deep inside we have trabecular bone (spongy bone), less regular structure where bone is organised in a mess work with lots of spaces in between
Describe the composition of the bone
- Protein: organic osteoid matrix (25%)
- Mineral (75%)
- Cells
Describe the composition of the organic osteoid matrix
What is the function of organic osteoid matrix?
The organic (osteoid) protein matrix • Mainly type 1 collagen • Gives both flexibility and tensile strength
Describe the composition of the bone mineral
What is the function of bone mineral?
• Hydroxy apatite
• Calcium and phosphate (Ca10(PO4)6(OH)2)
Rigid, brittle: gives high compressive strength
What are the 3 three main types of bone cells
- Osteoblasts
- Osteoclasts
- Osteocytes
What cells are found in bone marrow?
- Mesenchymal (stromal) stem cells which form osteoblasts which give rise to the osteocytes
- Haematopoietic stem cells which form all the different types of blood cells and osteoclasts
What are osteoblasts?
What are they derived from?
What do they promote?
- Bone forming cells
- Derived from mesenchymal stem cells
- Secrete osteoid, collagen matrix of bone
- Promote mineralization of osteoid – they lay down the Hydroxy apatite mineral so we end up with bone with high tensile and compressive strength
What are osteoclasts?
What are they derived from?
What do they form when they differentiate?
What do they promote?
- Bone reabsorbing cells
- Derived from haematopoietic stem cells
- Large, multinucleate
- During the differentiation of osteoclasts, cells fuse so they become a multinucleate, sinsitile unit, which attaches itself to the inner surface of the bone. This then forms a cavity to which they secrete acid and enzymes that digest the organic matrix. Acid dissolves the mineral component of bone and enzymes digest the organic component
- Secrete acid to dissolve bone mineral and enzymes to digest organic matrix
- Life cycle controlled by apoptosis
What are osteocytes?
What are they encased in?
what do they extend?
What is the function of Lacunocanalicular system?
What do they coordinate?
- Terminally differentiated osteoblasts – they form new bone and lay down organic osteoid and promote its mineralisation.
- Encased in bone mineral matrix (lacunae)
- Osteocytes extend multiple dendrites via minute canals in bone matrix (canaliculi)
- Lacunocanalicular system maintains communication with bone surface and blood vessels
- Thought to coordinate osteoblast and osteoclast activity
What is bone remodelling?
• It is a continuous process, that involves a balance between the osteoclasts and the osteoblasts
Describe the process of bone remodelling
- Osteoclasts attach to an inner section of the bone and secrete acid and digestive enzymes to reabsorb the bone.
- Osteoblasts then take over in the cavity and secrete osteoid which becombes mineralised to form new bone
- The processes are the same trabeculae bone and cortical bone
- The process begins with activation of osteoclasts
- It involves various stages of differentiation from hematopoietic stem cells into mature osteoclasts.
- They then attach to the bone surface and form a seal. They secrete acid and enzymes, forming cavities in the bone.
- The reverse of the cycle starts with osteoclasts apotosis, then the osteoblasts take over. There is an increase in differentiation from stromal cells which produces new osteoblasts which secrete osteoid which become mineralised to form new bone.
- The coordination of this process is under the control of the osteocytes, which tunes the activity between the osteoclasts and osteoblasts.
- Load bearing exercise it thought to play an important role
How is bone remodelling controlled?
• Load-bearing exercise leads to micro-stress fractures, detected by osteocytes, which then coordinate remodelling itself.
• Cytokines and other local signals. At the cellular level the control is via a network of signalling molecules promoting differentiation or apoptosis of osteoclasts and osteoblasts.
• At the systemic level, this local signalling can be coordinated by endocrine system: Endocrine
Oestrogen: inhibits osteocyte apoptosis, promotes osteoclast apoptosis. This tilts cycle to new bone formation rather than bone reabsorption
Oestrogen is essential for skeletal health.
Androgens
What is RANK?
What is this receptor stimulated by?
What is OPG?
RANK (receptor activator of nuclear factor kappa-B – surface receptor on immune cells ): surface receptor on pre-osteoclasts, stimulates osteoclast differentiation
This receptor is activated by RANK-ligand: produced by pre-osteoblasts, osteoblasts and osteocytes; binds to RANK and stimulates osteoclast differentiation
OPG (osteoprotogerin): decoy receptor produced by osteocytes; binds to RANK, preventing activation by RANK-L
Describe the Wnt signalling pathway
- Complex signal pathway, highly conserved, involved in animal development
- Drosophila wingless gene (1987)
- Required for osteoblast differentiation
- Negatively regulated by DKK (dickkopf) and sclerostin (SOST)
Frizzled is the Wnt receptor, and it requires a co-receptor, LRP5, to work. Regulation is via the co-receptor. SOST and LRP5 binding prevents Wnt activation. Wnt activation promotes bone formation (osteoblast differentiation) so this negative regulation acts as a brake.
