Bone Cell Biology Flashcards
What is the function of bone?
infrastructure
bone marrow (5% body weight)
reservoir of Ca and phosphate
specialized CT: realize the bone is calcified ECM
WHat cells are involved in bone?
osteoblasts
osteocytes
osteoclasts
What are osteoclasts activated by? inhibited by?
osteoclasts are
activated by PTH (parathyroid) (to relase and increase Ca)
inhibited by calcitonin (thyroid)
How much of bone is inorganic matrix, and what makes it up?
70%
Ca and phosphorous= hydroxyapatite
99% of boy’s Ca is stored in bone
what makes up the organic matrix of bone?
30%
osteoid
- type I collagen confers acid(eosin)ophilia
- proteoglycans: less than in cartilage
- glycoproteins: promote hydroxyapatitie
- osteocalcin, a bone specific glycoprotein, is one agent that romotes mineralization
what is osteocalcin and what does it promote?
a bone-specific glycoprotein that promotes mineralization
Compare these following components between bone and hyaline cartilage:
- mineral
- water
- collagen
- neuronal and vascular strucutres
- Mineral
- bone: 70%
- hyaline cartilage: none
- Water
- bone: 25%
- hyaline cartilage: 75%
- Collagen
- bone: type I
- hyaline cartilage: type II
- Neuronl and vascular structures
- bone: present
- hyaline cartilage: none
what are osteoblasts?
specialized fibroblasts
- bone morphogenic proteins (BMPs) and other growth factors induce differentiation from Mesenchymal Stem Cells (MSCs) into osteoblasts
Groups of osteoblasts make ________-
groups of osteoblasts make osteoid
- osteoid is type I collagen and glycoproteins-single osteoblasts can’t do this
Bone formation is completed by ________
bone formation is completed by deposition of Ca in the osteoid
what is hydroxyapatite essential for?
weight bearing. without it, there is no weight bearing
WHat is the “bone master gene” and what does kncoking it out produce
the bone master gene is Runx2. knocking out Runx2 prevents bone development
**note Runx2 and osteocalcin are osteoblast specific
where are osteocytes located? Osteocytes comprise what percentage of bone cells?
- occupy lacunae between lamellae of bone matrix, only one osteocyte per lacunae
- 90% of bone cells
- cytoplasmic “dendrites” penetrate the matrix and bind other osteocytes via gap junctions
What is the function of osteocytes and how long do they last?
- mechano-sensation, therby regulating bone remodeling
- secrete sclerostin, which inhibits Wnt signaling in osteoblasts, thereby stopping bone growth
- osteocytes live a long time! half life is 25 years!!
What is the function of osteoclasts? what are they and how do they form? where do they live?
- destroy bone matrix for remodeling and have ruffled borders that attach ECM, forming a microenvironment for bone resportion
- multinuclear bc of development from macrophage like cells that fuse together
- reside in hollowed-out areas of matric termed “Howship’s lacunae”
What is the significance of the ruffled borders of osteoclasts?
attach ECM, forming a microenvironment for bone resorption
WHat are osteoclasts regulated by?
hormones!!
- Calcitonin (thyroid) inhibits osteoclasts
- PTH (parathyroid) actiavtes osteoclasts
- lysosomes-cathepsin K-microenvironment
- Co2-H2CO3 (carbonic acid) - HCO3 (bicarb) + H- microenvironment optimized for bone resportion
- basically, carbon dioxide becomes carbonic acid which becomes bicarb and H which is the appropriate environment for bone resportion
What is this an image of?
Howships lacuna!
remember osteoclasts reside in howships lacuna
Bone is lined by outer and inner layer of connective tissue respectively termed _____ and _______
Periosteum and endosteum!!
outer=periosteum
inner= endosteum
Where are osteoblasts located?
periosteum, with small numbers in the endosteum
where are the osteocytes located?
lacunae of the bony matrix, which lies between the periosteum and endosteum
where are osteoclasts located?
most found attached to bony matrix on the endosteal side
What is the difference between compact and spongy bone
compact aka cortical (80% of long bone) is dense with no cavitation
spongy aka cancellous aka trabecular bone (20% of long bone) is cavitated
Flat bone vs long bone
- flat (calvaria): 2 plates of compact bone surrounding diploe of spongy bone
- long bones:
- diaphysis (shaft): compact with spongy bone lining marrow
- epiphyses (ends): caps of compact bone around spongy bone
what is the unit of bone structure?
the osteon which is a cylinder with concentric lamellae
lamellae have lacunae that do what 2 things?
lamellae have lacunae that
- harbor osteocytes
- are connected via canaliculi
what does the innermost lamella surround?
Haversian canal
What are the 2 ways by which bones can develop from primary bone to secondary bone (lamellar, mature)?
- intramembranous
- osteoblasts deposit osteoid onto a loos eframework of reticular connective tissue (not really a membrane)
- endochondral
- osteoblasts deposit osteoid onto cartilage
During endochondral development bone forms on what?
hyaline cartilage
what occurs at the diaphysis during endochondral development? how about at the epiphyses?
- diaphysis: osteoblasts invade calcified cartilage and secrete osteoid which leads to ossification
- epiphyses: same process, articular cartilage remains at the ends of the bone and epiphyseal plate cartilages remain v diaphyses and epiphyses, for growth in length
How do long bones get long?
- sex steroid hormones—- pituitary—– growth hormone (GH; somatotropin) —- liver—-IGF1—-epiphyseal plate
- zone of cartilage proliferation is activated by IGF-1
- zone of cartilage hypertrophy is where 20% of fractures occur
- zone of cartilage calcification (collagen X not collagen II)
- zone of ossification: eosinophilia due to deposition of collagen I by osteoblasts
How do fractures repair?
- macrphages remove debris
- fibroblasts and chrondroblasts secrete a fibrocatilaginous callus
- osteoblasts replace fibrocartilaginous callus with bony callus
- primary bone is repaced by lamellar secondary bone
how do we get a new skeleton every 10 years!
osteoclasts excavate bone which is then replaced by actiavted osteoblasts
what is osteopetrosis? what is osteoporosis?
- osteopetrosis: dense heavy bone; osteoclasts lack ruffled border
- psteoporosis: resorption by osteoclasts outpaces osteogenesis leading to hollow fragile bones
whats is osteoporosis? who gets it? what are they at risk for/ how do we prevent that?
therapeutic targets?
- 28 million americans with 2/3 women. postmenopausal lose 2% bone mass annually
- treatable, therapeutic targets are osteoclasts and osteoblasts
- at risk for breaks at wrist, hip and spine
- prevention:
- dietary Ca, vitamin D (improves absorption of Ca)
- weight bearing exercise
*
- prevention:
WHat is the screening test for osteoporosis?
- bone mineral density (BMD, grams/cm2)
- compare BMD with “young-normal” subjects
- T score= # of standard deviations below the young normal mean (note it declines with age)
how are osteoclasts produced?
- stromal cells in the bone marrow are induced by PTH to secrete 3 factors RANKL, OPG, and M-CSF. these act on monocytes
- M-CSF induces monocyte/macrophage proliferation
- RANKL (receptor for activator of nuclear factor kB ligand) induces differentiation into osteoclasts
- OPG= osteoprotegerin antagoizes RANK-L by binding to its receptor; hence OPG inhibits osteoclast production
Osteoblasts are inhibited by what? and induced by what?
osteoblasts:
- inhibited by leptin (obesity> risk for osteoporosis)
- induced by BMP
- induce by PTH
osteoclasts are inhibited by what and induced by what?
osteoclasts
- inhibited by calcitonin, osteoprotegerin
- induced by RANK-L
- induced by PTH
why is it weird that PTH induces osteoblasts and osteoclasts?
bc they are “opposing” bone cells
What are the anabolic drugs to treat osteoporosis?
-
PTH 1-34 teriparatide= Pro-osteoblast
- resolution of PTH paradox: “spikes” of PTH level, as attained by injection, favor osteoblast production, whereas constant PTH levels favor osteoclasts
- Anti-resorptive drugs= antiosteoclast
- SERMs (selective estrogen receptor modulators) raloxifene
- biphosphates: ibandronate (Boniva)
- mAbs (Denosumab) bind RANKL
- In pipelineL drugs with more specificty
- osteoclast inhibitor
- drugs that inhibit bidning osteoclasts to matrix
- anabolic agents such as Runx2
