090314 bone Flashcards
how is bone specialized CT?
it is CALCIFIED extracellular matrix
what is bone a reservoir of
Ca, phosphate
what 3 cell types are in bone?
osteoblasts
osteocytes (maintain bone)
osteoclasts (activated by PTH of the parathyroid, inhibited by calcitonin of the thyroid)
what is in the matrix of bone?
inorganic stuff is 70%
organic stuff is 30%
what’s in the inorganic stuff of the matrix of bone?
Ca + phosphorus = hydroxyapatite
what’s in the organic stuff of the matrix of bone?
type I collagen
proteoglycans (less than in cartilage)
glycoproteins (promote hydroxyapatite formation)
what does type I collagen stain
acidophilia, red
what is a glycoprotein that is bone specific?
osteocalcin
what is the organic matter of the matrix of bone called?
the osteoid
why is bone so hard?
combined hydroxyapatite AND collagen type I
diff btwn bone and cartilage?
bone has 70% hydroxyapatite/mineral content, whereas hyaline cartilage has none
bone is 25% water, hyaline cartilage is 75%
bone has type I collagen, hyaline cartilage has type II (softer) collagen
bone has neuronal and vascular structures, but hyaline cartilage has none
osteoblasts are what kind of cell
fibroblast (specialized)
the only osteoblast specific genes
Cbfa-1 (master gene transcription factor)
Osteocalcin
what growth factors induce osteoblast differentiation?
bone morphogenetic proteins (BMPs)
what do osteoblasts do?
make osteoid (type I collagen and glycoproteins)
how is bone formation completed?
osteocalcin-mediated deposition of calcium within the osteoid
what do osteocytes occupy
lacunae (1 osteocyte per lacuna)
what is the function of osteocytes
maintaining bone matrix
what runs in the canaliculi of lacuna?
the cytoplasmic processes of osteocytes (they extend to join those of other osteocytes via gap jxns)
role of osteoclasts
destroy or remodel bone matrix
what is special about the nucleus of osteoclasts
multinuclear-developed from macrophages that fused together
where do osteoclasts reside
hollow areas of matrix called Howship’s lacunae
what does the ruffled border of the osteoclast do?
attaches to ECM and provides microenvironment promoting bone resorption
how are osteoclasts regulated?
by HORMONES (calcitonin, PTH)
how does PTH activate an osteoclast
lysosomes manufacture cathepsin K, which is secreted into microenvironment; promotes secretion of acid, which activates the Cathepsin K
where are cells of bone located
osteoblasts-periosteum, with smaller numbers in endosteum
osteocytes-within lacunae of bony matrix between periosteum and endosteum
osteoclasts-mostly attached to bony matrix on endosteal side
compact bone
also called cortical bone
dense, no cavitation
spongy bone
also called cancellous, trabecular bone
has cavitations
microscopic appearance of compact vs spongy bone
identical
flat bone
2 plates of compact bone surrounding diploe of spongy bone
long bones
have diaphysis and epiphyses
diaphysis is compact with spongy bone lining marrow
epiphysis has cap of compact bone around spongy bone
osteon
cylinder in long bone with concentric lamellae
what does the innermost lamella in an osteon surround
Haversian canal
HOw are Haversian canals connected
volkmann’s canals
primary bone vs secondary bone
primary is immature (fetus, or broken bone, or in remodeling process)
secondary is mature/lamellar
two ways in which bone develops
intramembranous (osteoblasts deposit osteoid onto mesoderm)
endochondral (osteoblasts deposit osteoid onto cartilage)
endochondral bone development
bone forms on hyaline cartilage
at diaphysis-osteoblasts invade CALCIFIED cartilage–secrete osteoid to get ossification
at the epiphyses-same process as above. articular cartilage remains at ends of bones. epiphyseal plate cartilage remains for growth in length
for fetus development and natural repair of fractures
how do long bones get long (part one)
sex steroid hormones influence pituitary, which secretes growth hormone (GH/somatotropin), which caues liver to make somatomedin (or IGF-1), which goes to the epiphyseal plate
at epiphyseal plate:
there’s reserve cartilage, and beneath that-there’s a zone of proliferation, which is induced by somatomedin (IGF-1)
how do long bones get long (part two)
the zone of proliferation has chondrocytes
next is the zone of hypertrophy (20% of fractures)
how do long bones get long (part three)
next is the zone of calcification (basophilic), where you will find collagen X, not collagen II). This will be calcified cartilage.
next is the zone of ossification, which is eosinophilic due to the deposition of collagen I by osteoblasts
how does fracture repair occur?
macrophages remove debris
chondroblasts secrete callus of hyaline cartilage
osteoblasts replace cartilaginous callus with bony callus
primary bone replaced by secondary bone
what happens with difficult fractures that don’t heal?
they require grafting
what are therapeutic targets for osteoporosis
osteoclasts and osteoblasts
how are osteoclasts regulated by PTH?
stromal cells in bone marrow are induce by PTH to secrete three factors that regulate osteoclasts
the three factors are: RANKL, OPG, M-CSF
role of M-CSF
induces macrophage proliferation
RANK-L
induces macrophage differentiation into osteoclasts
OPG
osteoprotegerin - it antagonizes RANK-L by binding to its receptor
alpha5beta3
enalbes attachment of osteoclasts to bone
leptin has what action
inhibts osteoblasts
what is induced by PTH?
osteoblasts (when there’s spikes of PTH) and osteoclasts
anabolic drugs
pro-osteoblast
PTH 1-34 (teriparatide/Forteo)
anti resorptive drugs
anti-osteoclast
SERMs (raloxifene)
bisphosphonates (ibandronate/Boniva)
calcitonin
