Bone 2 -3 Flashcards
Ossification
Bone formation; bone that first appears as woven bone, which is eventually replaced by lamellar bone
Primary ossification center
First area to start ossifying
usually during prenatal development
located in diaphysis in developing long bones
Secondary ossification center
Appears after primary
usually during postnatal development
located in epiphyses in developing long bones
intramembranous ossification
develops from mesenchyme (no cartilaginous precursor)
direct mineralization of matrix secreted by osteoblasts
Flat bones of skull (frontal, parietal, etc), lacrimal, nasal, palatine, vomer, maxilla, mandible
Endochondral ossification
Has cartilaginous precursor (template of hyaline cartilage)
- Cartilage does not become bone! The cartilage model is replaced by bone
- Use long bone ossification as an example
Intramembranous ossification
1) Mesenchyme condenses and is highly vascularized
2) Mesenchymal cells differentiate into osteoblasts
3) osteoblasts secrete bone matrix (osteoid) to form trabecular
4) Trabeculae fuse together to form woven spongy bone
5) The periphery of the spongy bone will be remodeled into lamellar compact bone; deeper bone will be remodeled into lamellar spongy bone
When osteoblast gets surrounded by EC matrix it changes it’s name to
Osteocyte and can no longer secrete matrix bc there is no where for matrix to go
Endochondral Ossification Steps
1) Hyaline cartilage model is formed
2) Bone collar appears (around diaphysis)
Formed via intramembranous ossification within the perichondrium
Hollow cylinder of bone around the mid portion of the cartilage model
3) Chondrocyte in center hypertrophy, degernate and die. Cartilage matrix is calcified
4) Empty spaces are invaded by the the periosteal bud which is going to bring bring vasculature (vessels), mesenchymal cells, osteoprogenitor cells
5) Osteoprogenitors differentiate into osteoblasts, secrete osteoid on surface of calcified cartilage
6) Bone collar increases in thickness and length, but osteoclasts resorb the calcified cartilage and bone. Results in marrow cavity which will be populated with marrow cells
7) Secondary ossification centers form in a similar manner in the epiphyses
Epiphyseal plate
Cartilage remains at epiphyseal plate (to allow for growth in length until adulthood) and at the articular cartilage
Note: epiphyseal plates are hyaline cartilage
Endochondral ossification goal
growth in length and in width can occur. Growth in length is only possible while epiphyseal plate is present
Five zones of epiphyseal cartilage:
1) Zone of rest/reserve @ epiphysis
2) Zone of proliferation
3) Zone of maturation/hypertrophy
4) Zone of calcification
5) Zone of ossification @ diaphysis
Zone of Rest/reserve
Typical hyaline cartilage. Chondrocytes arranged randomly
Zone of proliferation
Chondrocytes undergo mitosis and are arranged in columns
Zone of maturation/hypertophy
Chondrocytes become enlarged, contain a lot of glycogen (white color) . Chondrocytes secrete alkaline phosphatase (marker of mineralization)
Zone of calcification
Cartilage matrix is calcified (purple color)
Chondrocytes are dying/dead due to calcified matrix. Leave empty lacunae
Zone of ossification (primary spongiosa)
Osteoprogenitors invade, differentiate into osteoblasts
Osteoblasts secrete matrix (osteoid) on surface of calcified cartilage
Matrix becomes calcified
Osteoclasts remove calcified cartilage and bone
Primary spongia (woven bone) is remolded into secondary spongiosa(lamellar bone)
Bone matrix
Very mineralized
Inorganic matter - 65% of dry weight. FOR HARDNESS & RESISTANCE
Consists of calcium and phosphorous (mostly ) also bicarbonate, citrate, magnesium, potassium, sodium
Hydroxyapatite crystals
Ca10(PO4)6(OH)2 calcium and phosphorous form
Non-crystalline in bone matrix
Calcium phosphate
Dont have a lot of calcium or phosphorous
bones won’t be hard
Hydroxyapatite crystals
Look like rods along collagen fibrils.
Give bones hardness and compressive strength
Hydratoin shell
Later of water around each hydroxyapatite crystal (surface ions of crystals are hydrated)
Facilitates ion exchange between the HA crystals and extracellular fluid B/w mineralized tissue and EC fluid
Bone matrix organic matter
36% of dry weight. For flexibility and strength.
Mostly type 1 collagen.
90% of organic matrix gives bone tensile strength
Triple helix, super coiled, typical 67 nm cross banding
Greater number of cross links between molecules than in non-bone tissue
Proteoglycans in organic matter
Give bone compressive strength.
Condroitin sulfate and heparin sulfate
Bone matrix noncollageous protein example alkaline phosphatase
may function in mineralization of osteoid
Blood serum levels increase during active bone formation which is used as a marker for bone formation
Other noncollageous proteins:
Cell attachment molecules: -fibronectin -Thrombospondin -Bone sialoprotein -Osteopontin Growth factors: -Fibroblast growth factors (FGFs) -Insulin-like growth facts (IGFs) -Transforming growth factors )Beta TGF-Beta -Bone morphogenic proteins (BMPs)
Bone cells which originate from mesenchymal
Osteocyte, osteoblasts, osteogenic cell (osteoprogenitor)
Bone cells which originate from meatopoietic (bone marrow, specialized macrophages)
Osteoclast
Osteoprogenitor cells
Mesenchymal stem cells
on bone surface (inner osteogenic layer of periosteum)
active during bone growth, factor repair, bone remodeling
Differentiate into osteoblasts (under the influence of TGF beta and BMP)
When you need osteoblasts what do you have?
TGF beta and BMP
Osteoblasts come from
Osteoprogenitor -> Preosteoblast -> osteoblast
Lines surfaces of bone tissue
Cannot be surrounded by bone matrix
Cuboidal to columnar shape when active in matrix synthesis; more squamous when less active
Functions of osteoblasts
Synthesis of unmineralized bone matrix (osteoid)
Osteoclas stimulating factos
Involved in matrix mineralization
If osteoblast is surrounded by bone matrix it becomes
osteocyte
if osteoblast is not surrounded by bone matrix it becomes
bone lining cells
Osteoblasts can become
osteocytes or bone lining cells
Osteoblasts secrete
osteocalcin and alkaline phosphatase
Matrix mineralization Steps
1) Osteocalcin and various glycoproteins bind Ca2+
2) Alkaline phosphatase and other enzymes in the matrix vesicles raise local concentration of PO4 -
3) Calcium phosphate and HA crystals form on matrix vesicles
4) Solid bony matrix is formed
In presence of PTH (parathyroid hormone), osteoblasts release..
macrophage colony-stimulating factor (M-CSF) that induces formation of osteoclast precursors
What differentiates into osteoclasts
Preosteoclasts differentiate into osteoclasts
Preosteoclasts have what on the cell surface?
Have RANK
Osteoblasts have what on surface?
RANKL
What happens when RANK binds to RANKL on osteoblast?
preosteoclast will mature into osteoclast
Release osteoclast-stimulating factor (OSF) does what?
activated osteoclasts to reabsorb bone
Osteopontin (OPN)
steals osteoclasts to bone so they can absorb bone
Steps to osteoblasts recruiting osteoclasts
1) Osteoblast secrete mCSF to induce the division of osteoclast presursors
2) Has rank ligand which binds to ligand on osteoclast precursor to tell it to differentiate to osteoclast
3) Activates the osteoclast
4) RANKL binds to RANK
5) Secretes OSF and OPN to activate osteoclasts
6) Inhibit osteoclast activity by producing OPG
Osteoprotogerin (OPG)
Produced by osteoblasts. Binds to RANKL and blocks RANK b/c when RANK binds to RANKL it will increase osteoclast activity
Inhibits differentiation of osteoclast precursors into mature osteoclasts
Regulates osteoclast activity
What increases rate of absorption aka osteoclasts
M-CSF, RANKL, OSF, OPN
What decreases rate of bone resorption
OPG
Osteocytes
When osteoblasts surround themselves with matrix, they become osteocytes
The space in the matrix for each osteocyte
Called lacuna
Tunnels for osteocytes
Osteocytes have long cytoplasmic processes, these are in tunnels called canaliculi (in order to get oxygen and nutrients)
Osteocytes nutrients, gas, waste exchange
Can’t occur through mineralized matrix.
Because osteocyte processes contact each other via gap junctions
Exchange using the gap junctions can provide nourishment for a chain of about 10 cells
Function of osteocyte:
- Maintain matrix
- Mechanosensory: detect mechanical loading and therefore need for bone increase or decrease
Osteoblast is
alkaline phosphatase positive
Lining cell
Alkaline phosphatase negative
Osteocyte
Alkaline phosphatase negative
Osteoblasts become osteocytes. 2 kinds:
1) Surronds itself with bone matrix = osteocyte
2) Doesn’t surround itself with bone matrix
Osteoclasts
Derived from bone marrow cells
Large, multi-nucleated, mobile
Have microvili
Sits on Howship’s lacuna when bone is removed
Howship’s lacuna
What osteoclast sits on
Bone remodeling (bone will be resorbed)
Done by basic multicellular unit (BMU), a wandering team of cells that dissolves an area of the bone surface that fills it with new bone
Remodeling follows which sequence
ART
Activation
Resporption and reversal
Formation and mineralizaition
How bone remodeling happens:
1) Activation of BMU
2) Resorption of bone by osteoclasts
3) F Formation of new bone by osteoblasts (process is reversed here and more bone is being added)
How does cortical bone remodel?
outside part :note
Remodels by osteoclastic tunneling
Osteoclastic resorption -> layering of osteoblasts -> formation of lamellae
Osteoclasts make up head of cutting cone, following by capillaries then osteoblasts which lay down osteoid will fill the cutting bone
Has blood vessel
How does spongy bone remodel?
Osteoclastic respiration and osteoblastic deposition of layers of lamellae
No osteons are formed (no concentric circles of lamellae around a vessel)
No blood vessels
Bone remodeling absorption and deposition..
an equal amount of bone respiration and deposition
No change in overall bone mass
Replace old bone with new bone
Bone modeling bone mass
changes in bone mass and changes in bone form
changes in size and shape due to resorption and deposition in unequal amounts and on different surfaces
Due to development and changes in loading patters
Bone growth causes length change because..
cartilage grows here
cartilage added by bone here
cartilage grows here
cartilage replaced by bone here
Remodeling growing shaft is remodeled by:
bone being resorbed at epiphyseal plate
bone added by appositional growth
Bone resorted
