Physiology of Bone Flashcards
Components of bone
- Cells
- Osteoid
- Extracellular matrix
- 95% type I collagen
- 5% ground substance
- Proteoglycans
- Extracellular matrix
- Minerals
- Crystaline hydoxyapatite
NOTE: The two main types of bone are cortical and trabecular
What factors lead to thickening of epiphyseal plate?
- Chondrocytes undergoing cell division
- Older chondrocytes enlarging
Dead chondrocytes are cleared away by ________.
Osteoblasts
NOTE: Osteoblasts invade space formerly inhabited by chrondrocytes and deposit bone matrix over the remnants of the disintergrating cartilage
Longitudinal growth of bones occurs at the________.
Epiphyseal plate
*Widening of the shaft of long bones occurs through the addition of layers to the exterior bone
Which factors stimulate the proliferation of chondrocytes?
- IGF-1
- FGF-2
- TGF-b
- IHH gene product
- PTHrP
- Cytokines
*Cytokines stimulate increased mitogen activity
NOTE: IGF-1, FGF-2, and TGF-b work in a synergistic fashion to increase chondrocyte growth. TGF-b AND PTHrP synergise to increase growth.
PTHrP and IHH inhibit _________ action to induce maturation of chondrocyts.
BMP (Bone morphogenic protein)
NOTE: BMP stimulate chondrocyte differentation. Growing chondrocytes differentiate into maturing chondrocytes that can differentiate into chondrocyte matrix, henceforth growing stops.
Which hormones stimulate chondrocyte proliferation?
PTH
GH (indirectly through IGF-1)
Estrogen (indirectly though IGF-1)
The local factor _________ induces hypertrophy and differentiation of chondrocytes.
BMP
Which hormones induce hypertrophy and differentiation of chondrocytes?
Thyroid hormone
Vitamin D
What is the mechanism of bone matrix being laid down over cartilage?
- Osteoclasts clear the dead chondrocytes
- Osteoblasts invade the chrondo-osseous junction and the cleared zone, and begin to lay matrix down aroung the disintergrating cartilage
- Blood growth into the area begins.
- Remodeling eplaces all cartilage matrix with bone matrix
- Mineralization of the bone matrix is initiated by proteins secreted by the osteoblasts. Mineralozation continues until normal bone density is reached.
What is the mechanism of non-growth plate dependent growth of bone?
- More new bone matrix is laid down on the outer surface of bone while more resorption occurs on the inner surface
- Net result: A widening of the bone shaft or enlargement of flat bones
NOTE: Non-growth plate areas include the shaft of long bones and all areas of flat bones
Sex steroids stimulate bone growth at puberty. Both estrogen and androgens act via the ____ receptor.
E
What are the stages of bone remodeling?
-
Reabsorptive phase
- Osteoclasts resorbing bone
-
Reversal phase
- Swtich from osteoclast activity to osteoblast activity
-
Formative phase
- Begin to lay down new matrix with osteoblasts
-
Completed phase
- New matrix has been laid and mineralization has been initiated at the initiation points
- After minerals precipitate out you have hydroxyappatite crystals
- New matrix has been laid and mineralization has been initiated at the initiation points
Bone remodeling occurs as the coordinated action of groups of bone cells known as the _________.
Basic Multicellular unit (BMU)
What are the steps of bone remodeling?
- Origination of the BMU
- Osteoclast recruitment
- Resoprtion of bone by osteoclasts
- Osteoblast recruitment to the BMU
- Osteoid formation
- Mineralization of the osteoid
- Quiescence
What factors play a role in origination of the basic multicellular unit (BMU)?
- Lining cells may be activated by:
- PTH
- Local cytokines
- Growth factors
- Mechanical stress
- Random events
What is the function of RANK?
- Stimulates the conversion of osteoclast precusor cells to osteoclasts
NOTE: The activity of RANK ligand is regulated by osteoprotegerin (OPG). OPG inhibits RANK ligand
_________ converts cell from monocyte/macrophage lineage preosteoclasts into preosteoclasts.
M-CSF
NOTE: When cells become preosteoclasts they are capable of producing RANK. RANKL must bind to RANK for the osteoblast to fuse and activate to become an osteoclast.
Parathyroid hormone stimulates the osteoblast to synthesize_______ and ___________.
M-CSF
RANKL
PTH blocks the synthesize of ___________.
Osteoprotegerin
Which factors stimulate resorption?
Intergrins
Interleukins
Vitamin A
NOTE: Osteoclasts attach to bone and pump in acid and digestive enzymes. Acid tends to remove the mineral and enzymes digest the matrix
How PTH stimulate bone resorption?
- Decrease the rate of osteoblast formation from preosteoblasts
- Increase osteroblast-mediated formation of osteoclast
Which factors can be used to measure bone resorption?
Urinary calcium
Hydroxyproline
Collagen cross-links
What role does Cbfa-1 play in bone remodeling?
Increases osteoblast recruitment
When is mineralization initiated?
When the osteoid reaches a thickness of approximately six mm.
As bone is completed osteoblasts are converted to _________ or _________ and their metabolic rate declines.
Osteocytes; lining cells
What type of stimulation can accelerate repair time in a bone fracture?
Electrical
