Bone Histology & Intramembraneous Ossification Flashcards

1
Q

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.

A
connective tissue
calcium
phosphorus
acidosis
homeostasis
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2
Q

two types of bone: ____ > first deposited and is remodeled by clasts and blasts into a ____

two types of mature: ____ or ____

A

immature/woven/fibrous
mature/lamellar

cortical/compant
trabecular/cancellous

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3
Q

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 ____.
A

lamellar
haversion
diaphysis
epiphyses

trabeculae
epiphyses
lamellar
haversion

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4
Q

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.

A
external
internal
flat
diploe
inner
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5
Q

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)
A

I

hydroxyapatite

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6
Q

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)

A

big fraction
70
macrophage

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7
Q

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 ____

A

endosteum
periosteum
mesenchymal
continuously

35
65

undifferentiated
cell division
isolated
bone

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8
Q

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

A
osteoprogenitor cells
cuboidal
columnar
polarized
controls
I
proteins

ER
mitochondria

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9
Q

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)

A
osteoblasts
differentiated
canaliculi
ECM
active
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10
Q

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

A
hydroxyapatite
I
hydroxyapatite
cartilage
brittle
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11
Q

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.

A

calcium phosphate
hydroxyapatite
insoluble
crystal growth inhibitors

alkaline phosphatase
collagen fibrils
nucleators

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12
Q

Mineralization: Formation of the Bone Mineral Matrix

• Mineralization occurs in the ECM between collagen fibrils – requires nucleators:

  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.

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 ____.

A

680
layers
bricks

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13
Q

Mineralization: Formation of the Bone Mineral Matrix

when collagen is mineralized, the fibers change in ____ and they get much ____

A

morphology

thicker

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14
Q

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

A

nucleator
pulses
lamellar

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15
Q

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.
A
hematopoietic
preosteoclast
premonocyte
surface
vascular system
preosteoclasts
multinucleated
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16
Q
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 ____

A
howship's lacuna
subosteoclastic
resorption
ruffled border
multinucleated
mitochondria

folded
surface
efficient

17
Q

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 ____

A

actin
osteopontin
alphaVbeta3
focal adhesion

18
Q

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 ____

A
carbonic anhydrase
H+
mitochondria
energy
CO2

proton pump
ATP
ATP
CO2

19
Q

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

A

CL-
HCl
bone/hydroxyapatite

chemical solution
biochemical/enzymatic

20
Q

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

A
homeostasis
osteoblast
M-CSF
preosteoclast/premonocyte
RANK
osteoblast
multinucleated
differentiation
21
Q

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

A

hormonal
PTH
increase
increase

osteoprotegrin
osteoprotegrin
RANKL

22
Q

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

A

active
active
calcification

active
quantity

deficiency
active
trabecular

23
Q

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).
A

perichondrium
articular
ligaments
tendons

fibrogenic
blood vessels
sharpey’s

osteogenic
embryo
postnatally
inactive

24
Q
Endosteum
• CT tissue.
• Covers \_\_\_\_ walls of the
bone marrow cavity.
• Extends into all the bone
cavities including the \_\_\_\_.
A

spongy

haversian canals

25
Q

Compact Bone

• Osteon (____):
• Basic structural unit of ____ bone.
• Cylinders of bone tissue formed from layers (____) of osteocytes and matrix arranged around a ____.
• Central canal is lined with ____ and contains a ____.
• Neurovascular bundle: artery, vein, nerve and lymphatic vessel.
• Osteocytes connected to each other and their blood supply by pseudopods
within ____.

  • Perforating Canals (____):
  • ____ branches of the central (Haversian) canal.
A
haversian system
compact
concentric lamellae
central (Haversian) canal
endosteum
neurovascular bundle
canaliculi

volkmann’s canals
perpendicular

26
Q

Compact Bone: Haversian Systems

mineralized matrix; impossible to supply nutrients by ____; in order to supply the osteocytes and remove waste, the organization is more complicated than cartilage

two osteocytes; down in left, capillary in haversian system; osteocytes have extensions that have ____ that connect cell body to capillary

the second cell is more problematic; processes bind to first cell via ____ (nutrients have to travel thrhough cytoplasm of one cell)

system works up to ____ microns (anymore, the cells would die); that’s why the haversion systems have ____ diameter

A
diffusion
canaliculi
gap junctions
100
short
27
Q

Spongy Bone

• Spongelike appearance formed by rods and plates of bone - ____:
• Spaces among the trabeculae are filled with ____.
• ____ but strong:
• Trabeculae develop along bone’s lines of
____.

no need for canaliculi beyond one or two layers, highly ____, caniliculi start at surface of bone marrow

A

trabeculae
bone marrow
lightweight
stress

vascularized

28
Q

Osteogenesis: Bone Formation

• Intramembranous Bone Formation:
– ____ and short bones: ____, ____.
– Requires:
• Well-____ primitive CT (mesenchyme).
• Bone formation is NOT preceded by the formation of a ____.
• Direct differentiation of cells within ____ into bone-forming cells (osteoblasts).

• Endochondral Bone Formation:
– Long bones: ____ and ____ skeleton.
– Replacement of a ____ template by bone.

The two processes can occur ____, and do, in the case of ____ healing and in the development of the ____ and the ____ which develop partially from intramembranous ossification and partially from endochondral ossification.

A
flat
skull
clavicle
vascularized
cartilage
mesenchymal condensation

axial
appendicular
hyaline cartilage

side by side
fracture
mandible
clavicle

29
Q

Stages of Intramembranous Ossification

  1. Condensation of ____ into soft sheet permeated with ____
  2. Deposition of osteoid tissue by ____ on mesenchymal surface; entrapment of first ____; formation of ____
A

mesenchyme
blood capillaries

osteoblasts
osteocytes
periosteum

30
Q

Stages of IM Ossification

  1. Honeycomb of bony trabeculae formed by continued mineral deposition; creation of ____ bone
  2. Surface bone filled in by bone deposition, converting spongy bone to ____ bone. Persistence of spongy bone in the middle layer
A

spongy

compact

31
Q

IM Ossification of the Skull

• Cranial ossification is ____ at birth.
• Soft regions of the skull called ____ are regions of ____
tissue.
• There are usually ____ fontanels at birth.
• Most fontanels close by ____ months and all
are usually closed by ____ months.

A
incomplete
fontanelles
dense irregular connective
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