Bone Development Overview Flashcards
What are the two developmental origins of bone?
Cranial neural crest
Mesoderm
Explain what osteoblasts and osteocytes are
Osteoblasts - cells which form bone and remodel bone. They are cuboidal cells and become embedded as they mature to form osteocytes.
Precursor forms the osteoblasts that make osteoid (unmineralised bone).
Once finished making bone, the osteocytes can form lining cells.
What are osteoclasts?
Attaches to bone via integrins.
Once attached, it makes a ruffled border and this is very there are proton pumps and chloride channels to make this an acid environment. The acid will demineralise bone.
When do osteoblasts and chondrocytes derive from?
From mesenchymal stem cells.
There are different genes such as Runx2 for bone cells and Sax9 for chondrocytes to form.
Where are osteoclasts derived from?
Haematopoietic stem cells
What are the two ways in which bone can form?
- Intramembranous ossification
- bone formed directly from precursors
- differentiation to osteoblasts - Endochondral ossification
- formation of cartilage model (perichondrium)
- cartilage mienralisation
- formation of bone
- primary and secondary ossification centre with the epiphyseal growth plate between
What cells need to communicate for bone remodelling?
Osteoblasts and osteoclasts
What are the 4 reasons why we remodel bone?
- Calcium homeostasis
- Maintenance of skeletal mass
- Response to mechanical loads/adaptation
- Altered remodelling during disease
How does remodelling occur?
Osteoclasts at the beginning are activation and resorb bone.
The osteoblasts can then proliferate and place down matrix and synthesise bone.
Name some hormones which work systemically, some growth factors and some transcription factors for bone remodelling
Systemically = parathyroid hormone, leptin, calcitonin, glucocorticoids
Growth factors = bone morphogenic proteins (BMPs), fibroblast growth factors, macrophage colony stimulating factor
Transcription factors = Runx2, osterix, Fos
How do the osteoblasts and osteoclasts interact?
Osteoclasts differentiate from mesenchymal cells.
Osteoblasts come from their own progenitor cells.
Receptors for PTH are on osteoblasts but act on osteoclasts to increase resorption.
Shows us osteoclasts are dependant on osteoblasts.
Osteoblasts only make bone where osteoclasts have previous resorbed. This is because the osteoblasts receive growth signals that osteoclasts have released.
How do osteoblasts mediate osteoclast differentiation?
Stem cell to make osteoclasts are controlled by an osteoblast.
Osteoblasts make MCSF (tells cell to become a macrophage).
Osteoblasts also make RANKL to drive the cell into an osteoclast.
Osteoblasts also make OPG which binds to RANKL to inhibit osteoclast differentiation.
What would happen if RANKL was taken out of a progenitor cell?
If you knock out RANKL - osteoclasts will not be produced.
The bones are totally calcified, they is no bone marrow.
No osteoclasts = called osteopetrosis.
What happens if OPG is knocked out a progenitor cell?
No osteoblasts so no bone formation.
This causes osteoporosis.
What are the 4 main stresses that a bone is under?
1) Compression
2) Tension
3) Torsion
4) Shear
What is meant by bones undergoing functional adaptation?
Our skeletons adapt to mechanisms forces that we put on them.
Osteocytes are the cells which control this adaptation.
What is Bunchem disease?
Thickened skull and long bones. No bone marrow. This is an osteoblast defect.
These patients had a loss of function of the Sost gene.
Scherostin is expressed in osteocytes, explain the importance of this
When bone is loaded, schlerostin is lost leading to increase in bone formation.
Schlerostin is an inhibitor of bone formation. When we knock it out, we get thicker bone.
Schlerostin inhibits WNT signalling.
Can knock it over with, mutation in patient, loading or though knocking out the gene.
What are the main two ways for bone overproduction?
Bone formation
No osteoclasts
What diseases can osteoclasts cause?
Osteoporosis
Osteopetrosis
Pagets disease
Rheumatoid arthritis
Why are osteoclasts important in periodontal disease?
PD - bone loss by osteoclasts due to inflammation
All the inflammatory cells make factors which affect osteoclasts to cause more resorption.
What disease can osteoblasts cause?
- Osteoschlerosis
- Osteosarcoma
- Osteogenesis imperfecta
What type of ossification do we have once a fracture has occurred?
Endochondral
