Biochemistry Of Bone Remodelling And Osteoperosis Flashcards
List the 4 main types of bone cells.
Osteogenic cells, osteoblasts, osteoclasts and osteocytes.
Describe osteoblasts and their function.
- mononucleated, basophilic and cuboidal in shape.
- Osteoblasts make bone.
- They synthesise uncalcified/unmineralised ECM called osteoid. This later becomes calcified/mineralised to form bone.
- become osteocytes when trapped in ECM
Describe osteocytes and their function.
- mononucleated, few organelles, ellipsoid cell body
- dendritic projections which can form gap junctions for communication
- maintain daily metabolism of bone including exchange of nutrients and waste with blood
- regulate function of osteoblasts and osteoclasts in response to mechanical and hormonal signalling
Describe osteoclasts and their function.
- edge of cell closest to bone has a ruffled border
- large and multinucleated
- powerful lysosomal enzymes and acids released to digest ECM
- removal/resorption of bone during normal development, maintenance and repair
Where are osteogenic cells usually found?
Alongside the membranes that surround the bones and the blood vessels in bone canals.
Where are osteoblasts derived from and where are they usually found?
- derived from osteogenic cells
- usually found in regions of bone formation (normal development or remodelling)
Where are osteocytes derived from and where are they usually found?
- when osteoblasts get trapped in ECM they become osteocytes
- found within matrix of bone
Where are osteoclasts derived from and where are they usually found?
- derived from fusion of monocytes present within bone marrow or other blood producing tissue
- lie in close contact with bone surface in resorption bays known as Howship’s lacunae
- mainly concentrated within layer of connective tissue found on inside of bone
What are Howship’s lacunae?
Resorption bays in close contact with the bone surface in which osteoclasts are usually found.
List some factors/molecules involved in osteoblast proliferation and differentiation.
- PTH (parathyroid hormone)
- glucocorticoids
- Wnt
- TGF-b
- hedgehog
- BMPs
- FGF
- IGF
What is sclerostin?
A negative regulatory protein produced only by mature osteocytes. It inhibits bone formation by osteoblasts and enhances apoptosis of osteoblasts.
What is osteoprotegerin?
A RANKL binding decoy cytokine that modulates RANK/RANKL interaction.
What is MCSF?
- Macrophage colony stimulating factor
- a survival factor for cells of monocyte/macrophage/osteoclast lineage
List some factors which regulate osteoclasts formation and activity.
- E2
- glucocorticoids
- PTH (parathyroid hormone)
- vitamin D3
- IL-1
- TNFa
- IFNy
What is RANKL?
- The receptor activator of NF-kB ligand
- member of TNF ligand family
- attaches to RANK to stimulate proliferation and differentiation of osteoclasts and inhibit their apoptosis
What is RANK?
- A receptor on the surface of osteoclasts and osteoclast precursors
- when RANKL binds to RANK, osteoclast proliferation and differentiation is stimulated and apoptosis inhibited
What is CBFA1?
- core binding factor alpha 1
- essential in osteoblast differentiation and bone formation
List some factors which can stimulate osteoblast expression of RANKL.
- TNF-a
- PTHrP (parathyroid hormone related peptide)
- IL-1
- IL-11
- Vitamin D
- glucocorticoids
- PTH
- PGE2 (prostaglandin E2)
Describe the bone remodelling cycle.
Quiescence > osteoclast recruitment, differentiation, activation > resorption > osteoclast apoptosis, removal > reversal > osteoblast recruitment, differentiation, activation > matrix synthesis > formation > mineralisation > quiescence
Does OPG stimulate or inhibit osteoclast formation?
Inhibits by binding to RANK so that RANKL cannot.
How are Wnt proteins involved in bone formation and resorption?
- act on osteoblast precursor cells and promote differentiation into mature osteoblasts
- suppress bone resorption by regulating RANKL/OPG ratio
How do osteoclasts bind to bone matrix?
Via integrins
What do osteoclasts secrete do resorb bone?
Acid and cathepsin K
When does primary mineralisation occur?
Within the first 100 days following remodelling.
When does secondary mineralisation occur?
From approx day 101 to 3 years
List 5 systemic hormones which stimulate bone remodelling.
- parathyroid hormone
- 1,25 dihydroxyvitamin D
- parathyroid hormone related protein
- growth hormone
- thyroid hormone
List 7 locally acting factors which stimulate bone remodelling.
- interleukin-1
- tumour necrosis factor (TNF)
- insulin like growth factor
- interleukin-6
- RANKL
- prostaglandins
- M-CSF
List 4 systemic hormones which inhibit bone remodelling.
- oestrogens
- androgens
- progesterone
- calcitonin
List 5 locally acting factors which inhibit bone remodelling.
- OPG
- mechanical loading
- interferon gamma
- IL-4, -10, -13 -18
- transforming growth factor beta
During puberty, which sex typically acquires more bone mineral density first?
Females
What are some determinants of peak bone mass?
Lifestyle, genetics, hormones and nutrition
How does spinal bone change in adolescents?
Increases in size and trabecular thickness
How do long bones change in adolescents?
Increase in length and diameter
What are the three phases of age related changes in bone mass?
- Attainment of peak bone mass (from birth until late 20s/30)
- Consolidation (from late 20s - early 40s)
- Age related bone loss (from 40s until death)
Why are women more like to cross the fracture threshold during age related bone loss?
They have a lower peak bone density than men do plus after menopause the decrease in oestrogen makes them more susceptible.
List some biochemical markers of bone formation.
- bone specific alkaline phosphatase
- type 1 collagen pro-peptides (carboxyterminal and amino terminal)
- serum osteocalcin
State a biochemical marker of bone resorption.
Serum or urine levels of N terminal and C terminal cross linked telopeptides. These can be used to assess fracture risk.
