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

Bone Cell Biology Flashcards by Allison Cotter

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

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WHat cells are involved in bone?

osteoblasts

osteocytes

osteoclasts

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What are osteoclasts activated by? inhibited by?

osteoclasts are

activated by PTH (parathyroid) (to relase and increase Ca)

inhibited by calcitonin (thyroid)

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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

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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

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what is osteocalcin and what does it promote?

a bone-specific glycoprotein that promotes mineralization

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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

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what are osteoblasts?

specialized fibroblasts

bone morphogenic proteins (BMPs) and other growth factors induce differentiation from Mesenchymal Stem Cells (MSCs) into osteoblasts

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Groups of osteoblasts make ________-

groups of osteoblasts make osteoid

osteoid is type I collagen and glycoproteins-single osteoblasts can’t do this

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Bone formation is completed by ________

bone formation is completed by deposition of Ca in the osteoid

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what is hydroxyapatite essential for?

weight bearing. without it, there is no weight bearing

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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

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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

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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!!

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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”

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What is the significance of the ruffled borders of osteoclasts?

attach ECM, forming a microenvironment for bone resorption

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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 1. harbor osteocytes 2. 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)?

1. intramembranous 1. osteoblasts deposit osteoid onto a loos eframework of reticular connective tissue (not really a membrane) 2. endochondral 1. 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?

1. macrphages remove debris 2. fibroblasts and chrondroblasts secrete a fibrocatilaginous callus 3. osteoblasts replace fibrocartilaginous callus with bony callus 4. 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 *

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**