Bone Histology & Intramembraneous Ossification Flashcards
Bone Properties
• Specialized form of ____ with a mineralized collagen matrix.
• Bones are units of the skeletal system.
– Individual bones are made up of bone tissue, marrow, cartilage and periosteum
• Physical properties:
– Strength: resistance to compression, shear and tensile strength.
– Reservoir of ____ and ____.
– Adaptable to growth and weight changes by remodeling.
– Able to self-repair.
• Functions:
– Protection for brain and internal organs.
– Attachment sites for muscles allowing movement of limbs.
– Defense against ____.
– Endocrine ____.
– Hearing.
connective tissue calcium phosphorus acidosis homeostasis
two types of bone: ____ > first deposited and is remodeled by clasts and blasts into a ____
two types of mature: ____ or ____
immature/woven/fibrous
mature/lamellar
cortical/compant
trabecular/cancellous
Bone Types: Compact Bone and Spongy Bone
- Compact Bone:
- Does not have spaces or hollows in the bone matrix that are visible to the eye.
- ____ and ____.
- Thick-walled the ____ of long bones.
- ____ of long bones.
- Spongy Bone (a.k.a. trabecular bone or cancellous bone):
- Delicate network of ____ which branch and intersect to form a sponge-like tissue.
- ____ contain mainly spongy bone.
- ____ but NOT ____.
lamellar
haversion
diaphysis
epiphyses
trabeculae
epiphyses
lamellar
haversion
Structure of a Flat Bone
• ____ and ____ surfaces of ____ bones are composed of compact bone.
• Middle layer is spongy bone and it is also called the ____.
• An impact to the skull may fracture the outer layer and crush the spongy bone, but not harm ____ compact bone or the underlying brain.
external internal flat diploe inner
Bone Components
• Cells – Osteoblast lineage: • Osteoprogenitor Cells • Osteoblasts • Osteocytes – Monocyte-macrophage lineage: • Osteoclasts
• ECM: – Organic (osteoid): –-- Fibers: Type \_\_\_\_ Collagen. –-- Ground substance: GAGs, PGs. – Mineral: –-- \_\_\_\_ (Ca10(PO4)6(OH)3)
I
hydroxyapatite
Bone Components
table: mineral component is ____ of total part of bone > of hydroxyapatite > ____%
OPC > blasts > cytes
monocyte (from bone marrow) > macrophage (involved with phagocytosis) > clasts (a type of ____, engulf the mineral and organic matrices of the bone)
big fraction
70
macrophage
Osteogenic Lineage
• Osteogenic Cells: • Found in the \_\_\_\_ and \_\_\_\_. • Arise from embryonic \_\_\_\_ cells. • Multiply \_\_\_\_ and differentiate into osteoblasts in response to stress or fractures.
- Osteoblasts:
- Produce an ECM of about ____% collagen fibers and ____% mineral (mostly calcium phosphate).
• Osteocytes:
• Osteoblasts that have completely surrounded
themselves with the extracellular matrix they produce.
ostoegenic are ____; capable of mitosis, continuously divide
osteocyte uncapable of further ____; differentiation stops
Spicules = ____, newly formed pieces of ____
endosteum
periosteum
mesenchymal
continuously
35
65
undifferentiated
cell division
isolated
bone
Bone Cells: Osteoblast
• Derived from ____.
• Epithelial-like ____ or ____ in monolayers at sites of active bone
formation.
• ____ cell: ECM released at the cell/bone interface.
• Synthesizes the organic matrix (osteoid)
and ____ mineralization of the matrix:
• Osteoid:
–• Type ____ collagen.
–• PGs.
• Non-collagenous ____.
osteoblast has features of actively secreting cell; big ____ and secretory vesicle and lots of ____; because it’s producing osteoid
osteoprogenitor cells cuboidal columnar polarized controls I proteins
ER
mitochondria
Bone Cells: Osteocyte
• Derived from \_\_\_\_. • Terminally \_\_\_\_: Incapable of cell division. • Highly branched cell with cytoplasmic extensions entering the \_\_\_\_ of the bone matrix. • Maintains the bone \_\_\_\_.
very ____ cell (biochemically, metabolically)
osteoblasts differentiated canaliculi ECM active
Osteogenic Cells: The Bone Mineral Matrix
• Inorganic (65%) – \_\_\_\_ (a form of calcium phosphate) • Organic (35%) – Type \_\_\_\_ Collagen – Non-collagenous proteins: • Osteocalcin, osteopontin, osteonectin • Bone sialoprotein • Growth factors, cytokines
– GAGs
• Chondroitin sulfate
• Keratan sulfate
• Hyaluronic acid
most of matrix of bone is mineral = ____
take a bone, and do not mineralize, you end up with an element similar to ____
if only mineral and no collagen > the bone becomes very ____, the bone would break easily and it is not resistant to impact/stresses
hydroxyapatite I hydroxyapatite cartilage brittle
Mineralization: Formation of the Bone Mineral Matrix
- Mineralization: precipitation of ____ and growth of crystals of ____.
- Calcium phosphate is extremely ____ and precipitates at high concentrations of calcium or phosphate ions.
- In non-mineralizing tissues, calcium phosphate precipitation is prevented by ____ (e.g. pyrophosphate).
• In mineralizing tissues (e.g. bone), pyrophosphate is destroyed by ____.
• Mineralization occurs in the ECM between ____ – requires ____:
1. Within the holes that separate the collagen molecules within the collagen fibrils.
2. Between adjacent collagen molecules within the fibril.
3. Space between adjacent fibrils.
calcium phosphate
hydroxyapatite
insoluble
crystal growth inhibitors
alkaline phosphatase
collagen fibrils
nucleators
Mineralization: Formation of the Bone Mineral Matrix
• Mineralization occurs in the ECM between collagen fibrils – requires nucleators:
- Within the holes that separate the collagen molecules within the collagen fibrils.
- Between adjacent collagen molecules within the fibril.
- Space between adjacent fibrils.
Molecular arrangement of collagen and hydroxyapatite crystals in compact bone.
(a) Collagen fibers overlap adjacent fibers as they repeat every ____ Å.
(b) Hydroxyapatite crystals
(Ca10[PO4]6[OH]2) are arranged in ____ within each fiber, resembling overlapping ____.
680
layers
bricks
Mineralization: Formation of the Bone Mineral Matrix
when collagen is mineralized, the fibers change in ____ and they get much ____
morphology
thicker
Osteoblast Biology: The Bone Mineral Matrix
Edge of matrix acts as ____; layers of matrix; osteoblasts produce matrix in ____; these layers are known as ____ bone; similar to growht rings of tree
nucleator
pulses
lamellar
Bone Cells: Osteoclast
• Derived from a pluripotent ____ stem cell (granulocyte/macrophage colony forming unit, GM- CFU).
- The monocyte progenitor cell may differentiate into either ____ or ____.
- Preosteoclasts travel directly through the marrow to the trabecular bone ____, or via the ____ to the cortical bone.
- Mature osteoclasts arise by fusion of ____ to form a ____ giant cell.
- Responsible for bone resorption associated with bone modeling, remodeling and pathology.
hematopoietic preosteoclast premonocyte surface vascular system preosteoclasts multinucleated
Bone Cells: Osteoclast  1. Highly polarized cell: active side forms a cavity (\_\_\_\_ a.k.a \_\_\_\_ compartment or \_\_\_\_ bay). 2. Active surface shows a \_\_\_\_. 3. Sealing zone. 4. \_\_\_\_ cell, rich in \_\_\_\_.
ruffled border > plasma membrane at place of contact is actually highly ____ > same way as microvill increase absorption; the presence of ruffled border also increases____ in contact > making the dissolving a lot more ____
howship's lacuna subosteoclastic resorption ruffled border multinucleated mitochondria
folded
surface
efficient
Osteoclast
sealing zone, isolating the cavity from the nonactive part of the osteoclast > it is a structrue that binds the cell (____) with non-collagen protein ____ on the bone matrix (mediated via an integrin receptor > ____); sealing zone is a ____
actin
osteopontin
alphaVbeta3
focal adhesion
Osteoclast
____ > capable of catalyzing rxn to produce carbonic acid (from CO2 + H2O); in water, dissociates into bicarbonate and ____; where does CO2 come from? > TCA cycle, from the ____; two reason for abundance of mito in clasts: to produce lots of ____, and it also needs a lot of ____
H+ ions leave the cells via a ____ in the ruffle border (against gradient); mediated by ____ (active pump); spending a lot of energy to pump the H+; high levels of ____ also produces high level of ____
carbonic anhydrase H+ mitochondria energy CO2
proton pump
ATP
ATP
CO2
Osteoclast
exports bicarbonate for another ion: imports one ____; since Cl is negatively charged, and since a lot of positive in howship’s lacuna, will attract the Cl in order to null the charge (the pump doesn’t require energy) > formation of ____ (howship’s lacuna is very acidic = 4.5)
in acidic conditions the ____ dissolves away
the cell is highly secretory; secretes ____ that destroys the osteoid
by two mechanisms: ____ of HCl, and ____ degradation by producing proteases
CL-
HCl
bone/hydroxyapatite
chemical solution
biochemical/enzymatic
Osteoblast/Osteoclast Cross-talk: Coupling
bone is involved in ____ of pH of blood
sometimes, bone is resorbed just for calcium/phosphate ions
center of regulation = ____; regulates the whole equilibrium
monocytes express: ____ receptor; can bind M-CSF; when receptor binds the ligand, induce the differentiation of monocyte into ____
the ligand is produced by the osteoblast; induces the preosteoclast to express a different receptor > ____; the ligand is RANKL, produced by the ____
upon binding of RANK to RANKL, formation of ____ cell, osteoclast finishes ____ and finds place on bone on where to attach
homeostasis osteoblast M-CSF preosteoclast/premonocyte RANK osteoblast multinucleated differentiation
Osteoblast/Osteoclast Cross-talk: Coupling
must exist an equilibrium; osteoblast is control by other mechanism; ____ control (parathyroid hromone) > produce the MCSF and RankL; in presence of ____, ____ in differentiation of osteoclasts; ____ reabsorption of bone
osteoblast also produces ____; a decoy protein, can bind RANKL with higher affinity than RANK itself; blocks RANKL, no differentiation of mature osteoclasts; however, PTH, also blocks the synthesis of ____; ____ is now free to interact with osteoclasts
hormonal
PTH
increase
increase
osteoprotegrin
osteoprotegrin
RANKL
Osteoblast/Osteoclast Disequilbirum Disorders
Osteopenia:
Cause: osteoblasts are not ____ enough and/or osteoclasts are too ____
Results in decreased ____ or density of bone
Osteoporosis
Cause: osteoblast are not ____ enough
Results in progressive reduction in ____ of bone
Osteopetrosis
Cause: osteoclast ____ or no ____ OC
Results in excessive formation of dense ____ bone
active
active
calcification
active
quantity
deficiency
active
trabecular
Periosteum
- Functionally and embryologically similar to the ____.
- Covers outer surface with the exception of ____ surfaces and ____ and ____ attachments.
- Two layers:
- Outer layer (____):
- ____ (some entering the Volkmann’s canals).
- ____ fibers.
• Inner layer (\_\_\_\_): • \_\_\_\_ and \_\_\_\_: Osteoprogenitor cells. • Adult: \_\_\_\_ CT cells with osteogenic potential (bone injury and repair).
perichondrium
articular
ligaments
tendons
fibrogenic
blood vessels
sharpey’s
osteogenic
embryo
postnatally
inactive
Endosteum • CT tissue. • Covers \_\_\_\_ walls of the bone marrow cavity. • Extends into all the bone cavities including the \_\_\_\_.
spongy
haversian canals