Bone modelling, remodelling and RANKL/RANK/OPG pathway Flashcards
What are the 2 methods of bone modelling/growth, and what do they increase?
Longitudinal growth causes increase in length
Appositional growth causes increase in width/diameter
Where is the main site of longitudinal growth of bone?
Growth plate
What are the 3 zones of the growth plate, and where is each zone located in the growth plate?
Proliferation zone is closest to epiphyseal side
Hypertrophic zone is in the middle of the other 2 zones
Ossification zone is closest to the diaphyseal side
What occurs in the proliferating zone of the growth plate during longitudinal growth of a bone?
Proliferating chondrocytes undergo interstitial growth by forming new cartilage inside the existing cartilage (growth plate)
What is interstitial growth of cartilage?
New cartilage produced inside existing cartilage
What occurs in the hypertrophic zone of the growth plate during longitudinal growth of bone?
Mature chondrocytes enlarge and degenerate
What occurs in the ossification zone of the growth plate during longitudinal growth of bone?
Dead/dying chondrocytes are calcified, so this layer becomes fragile and disintegrates and is replaced by new bone
In longitudinal growth, what part of the bone structure is elongated?
Diaphysis
When does the growth plate become the epiphyseal line?
After puberty
What is epiphyseal fusion?
Replacement of growth plate by epiphyseal line after sexual maturation and bone has grown to full length
After epiphyseal fusion, does the bone still grow?
Bone can only grow by appositional growth
How does epiphyseal fusion occur after bone has grown to full length?
Chondrocytes stop proliferating and growth plate is ossified
What is bone modelling?
Processes of bone growth that change individual shape of bone, that involves osteoclasts and osteoblasts
Why is appositional growth balanced by osteoblastic and osteoclastic activity?
Prevents bone from becoming too bulky/weak
What osteoclastic activity occurs during appositional growth of the bone?
Lining of medullary cavity resorbed
Why do osteoclasts resorb the medullary cavity lining in appositional growth of bone?
So that medullary cavity diameter increases as the bone grows
What osteoblastic activity occurs in appositional growth of bone?
Osteoblasts produce tissue under periosteum
By which process does the tissue under periosteum change into bone in appositional growth?
Intramembranous ossification, where bone is formed from connective tissue
What is the rate of longitudinal growth compared to rate of appositional growth of bone?
Longitudinal at faster rate than appositional
What is bone remodelling?
Cell turnover of bone that occurs after longitudinal growth arrest at epiphyseal fusion
What 2 processes cause bone remodelling?
Bone resorption by osteoclasts
Bone formation by osteoblasts
What are the 4 phases of bone remodelling?
Activation, Resorption, Reversal, Formation
What happens in the activation phase of bone remodelling?
Resting bone surface is converted to remodelling surface which attracts osteoclast precursors that now fuse into large, multinucleated osteoclasts
What 2 processes do osteoclasts use in the resorption phase of bone remodelling?
Osteoclasts resorb bone matrix by acidification and proteolytic digestion
In which specific structure does resorption occur in the resorption phase of bone remodelling?
Howship’s lacunae (scallop-shaped depression)
After bone resorption has occurred in the resorption phase of bone remodelling, what 2 things happen?
Calcium released into bloodstream
Osteoclasts leave resorption site or undergo apoptosis
What happens in the reversal phase of bone remodelling?
Osteoblasts recruited to remodelling surface
What happens in the formation phase of bone remodelling?
Osteoblasts secrete osteoid, which is the basis for mineralisation, then matrix hardens to form bone
What pathway is used to regulate bone remodelling?
RANK/RANKL/OPG pathway
What is RANK?
Receptor on osteoclast precursor that binds to RANKL to stimulate osteoclast proliferation and bone resorption
What is RANKL?
Cytokine that binds to RANK receptor to promote osteoclastic activity, so is a key mediator of bone resorption
What is Osteoprotegerin (OPG)?
Glycoprotein produced by osteoblasts, that inhibits bone resorption by inhibiting osteoclast formation, and promotes bone formation
How do RANKL and OPG work antagonistically in bone remodelling?
OPG can bind to RANK and block RANKL from binding, which inhibits osteoclastic activity
If RANKL binds to RANK then osteoblastic activity is inhibited
How can alterations of the RANKL/OPG ratio be harmful?
Increased bone resorption is cause of some bone diseases
