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
_________ 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.
