Cellular structure of bone Flashcards
Hydroxyapatite
The principle mineral component of bone, composed of calcium and phosphate (Ca10(PO4)6(OH)2). Responsible for the hardness of bone.
Osteoblast
Bone cells responsible for forming osteoid and controlling its mineralization.
Osteocyte
Terminally differentiated osteoblast encased within mature bone. Thought to be the master regulators of bone remodelling.
Osteoclast
Large, multi-nucleate cells responsible for reabsorption of bone tissue.
Osteoid
The organic matrix of bone, consisting mainly of collagen and other protein. Secreted by osteoblasts, which line the surface of newly-formed bone. Osteoid is initially flexible, like cartilage, but the process of mineralization, also controlled by osteoblasts converts it into the strong and dense mineralized tissue of the skeleton.
Remodelling
The skeleton is continually renewed throughout life by bone remodelling, a process whereby old bone is broken down (reabsorbed) by osteoclasts in a coordinated cycle of new bone formation by osteoblasts
Functions of bone pt 1
- Support and movement: attachment site for muscles
- Protection for internal organs
- Provides home for bone marrow
- Acts as mineral reservoir
- Endocrine: source of some ‘non-classical’ hormones
Bone structure
- Cortical (compact) bone
* Trabecular (spongy, cancellous) bone
Bone composition
- Protein: organic osteoid matrix (25%)
- Mineral (75%)
- Cells
Organic (osteoid) protein matrix
- Mainly type 1 collagen
* Gives both flexibility and tensile strength
Bone mineral
- Hydroxy apatite
- Calcium and phosphate (Ca10(PO4)6(OH)2)
- Rigid, brittle: gives high compressive strength
Bone cells
- Osteoblasts
- Osteoclasts
- Osteocytes
- Bone marrow cells
Bone marrow cells
- Mesenchymal (stromal) stem cells
* Haematopoietic stem cells
Osteoblasts
- Bone forming cells
- Derived from mesenchymal stem cells
- Secrete osteoid, collagen matrix of bone
- Promote mineralization of osteoid
Osteoclasts
- Bone reabsorbing cells
- Derived from haematopoietic stem cells
- Large, multinucleate
- Secrete acid to dissolve bone mineral and enzymes to digest organic matrix
- Life cycle controlled by apoptosis
Osteocytes
- Terminally differentiated osteoblasts
- Encased in bone mineral matrix (lacunae)
- 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
Bone remodelling
Three major types of cells constitiute bone tissue: osteoclast are bone absorbing cells derived from a monocyte lineage of the hematopoietic tem cells, osteoblasts are bone forming cells descended from the mesenchymal stem cells, and osteocytes are bone matrix embedded cells originated from osteoblasts. Mature quiescent osteoblasts on the bone surfaces are distinguished as bone lining cells.
Control of remodelling
- Load-bearing exercise
- Cytokines and other local signals
- Endocrine
Hormones involved in remodelling
- Oestrogen: inhibits osteocyte apoptosis, promotes osteoclast apoptosis
- Oestrogen is essential for skeletal health
- Androgens
Induction of steoclast differentiation by RANK ligand
- RANK (receptor activator of nuclear factor kappa-B): surface receptor on pre-osteoclasts, stimulates osteoclast differentiation
- 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
Wnt signalling pathway
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 (osteoblasts differentiation) so this negative regulation acts as a brake.
Diseases of bone
Mutations affecting key signals • Very rare, but have elucidated mechanisms Less rare • Osteomalacia Common • Osteoporosis
Bone diseases caused by mutation
Osteoporosis pseudoglioma
Sclerosteosis and van Buchem disease
Osteopetrosis
•
Osteoporosis
- Loss of bone density
- Increased fracture risk
- Increase in bone resorption over formation
Osteoporosis pseudoglioma
Inactivation of LRP-5, wnt co-receptor
Sclerosteosis and van Buchem disease
Mutation of SOST gene, inactivating sclerostin
Osteopetrosis
Mutation inactivates RANKL protein
