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48 Cards in this Set

  • Front
  • Back
Functions of Bone
-skeleton supports muscle and bears weight of the body

-protects vital organs (CNS, heart, lungs, etc.)

-act as levers during muscle contraction

-important reservoir of minerals
Architecture of Bones
-consists of 2 epiphyses (heads), a diaphysis (shaft), and metaphyses

-METAPHYSES = cone-shaped portion joining epiphyses to diaphysis

-long bone growth - contains columns or trabeculae of cartilage and bone
Diaphysis (shaft)
-contains central marrow (medullary) cavity

-mostly surrounded by compact cortical bone
Epiphysis (head)
consists mostly of spongy bone with a shell of compact bone around it

-articular surface covered by hyaline cartilage
-transition between epiphyses and diaphyses
Compact Bone
-dense, solid, and cortical

-no marrow tissue, does possess vascular connective tissue
Cancellous Bone
-spongy bone composed of slender, irregularly shaped trabeculae or bars of calcified matrix to form network

-a lot of soft connective tissue - occupies the marrow spaces between the trabeculae
Bone Marrow
-soft tissue between trabeculae of cancellous bone

-w/i central medullary cavity

-red (hemopoietic tissue) or yellow (fatty marrow)
- Fibrous CT which covers the outer suface of cortical bone

- NOT found over articular cartilage or where ligaments and tendons insert

- Contains an outer fibrous layer AND inner cellular layer
Sharpey's Fibers
-periosteal collagen fibers penetrate the outer region of bone matrix

-binding the periosteum to bone
- Counterpart to periosteum

- Lines the inner surface of bone and surrounds the central medullary cavity

- It has osteogenic AND hempoietic potential
- This is layering of mineralized matrix

- Regular orientation of collagen fibers w/i each layer

- Adjacent layers of collagen fibers oriented at different angles
Study Techniques
Two techniques -

1) GROUND SECTIONS - destroys all soft tissue elements, including bone cells

- Retains mineral content but lose soft tissue
- Thus lacunae and canaliculi appear empty, black


- Bone not decalcified (or partially) stain basophilic because of calcium salts.

- Decalcified bone stains eosinophilic due to high content of type I collage and low concentration of sulfated GAGs.
- Differentiate from mesenchymal cells.

- They have prominent vesicular nuclei, tall columnar (as desecribed as epithelioid).

- Found on bone surfaces with growth potential.

- Produces osteoclast-differentiating factor - promote osteoclastogenesis.

- Associated w/ bone formation.

- In cellular layer of periosteum, in endosteum, and as a rim around trabeculae.

- Communicate by gap junctions.

- Secrete bone matrix (osteoid), participate in mineralization of matrix and bone resorption

- Produce paracrine and autocrine factors for recruitment of osteoprogenitors and regulation of osteoclastic matrix resorption.

- Responds to endocrine factors.

- Have receptors for cytokines, PTH, Vitamin D3, and estrogen --> for bone turnover (none for calcitonin)

- Stromal osteoblasts major source of cytokines (which are stimulators for bone resorption)
- Osteocytes are osteoblasts trapped w/i matrix (osteoid) which they secrete.

- They occupy lacunae (small spaces) w/i calcified matrix.

- Organic matrix (osteoid) calcifies to become bone (mineralized matrix).

- Completely fill lacunae in living state but shrink during tissue processing
--> creates ARTEFACTUAL SPACE btw cells.

- CANALICULI radiate from lacunae and link osteocytes.

- Canaliculi contain extracellular fluid-caries nutrients and metabolites to nourish osteocytes and exchange btw osteocytes and blood vessels.

- Gap junctions of adjacent cytes permit passage of hormones, ions in a "bucket-brigade" fashion.

- Osteoblast-osteocyte complex exist around periphery of bone.

- They maintain bone matrix by transporting inorganic ions between blood and matrix.

- OSTEOCYTIC OSTEOLYSIS - Ca2+ pumps pull Ca out canaliculi fluid into plasma --> increases dissociation of Ca from Ca-phosphate
- Large, multinucleated cells derived from bone marrow stem cells (also precursors to monocytes).

- Motile with numerous cell processes.

- Located in depressions on bone surface known as HOWSHIP'S LACUNAE or resorption cavities.

- Attachment of cells to matrix performed by integrin receptors.

- Contains several regions (basal zone, clear zone, vesicular zone).
Osteoclastic Lysosomal Enzymes
- Found in ER, Golgi, and transport vesicles of osteoclast.

- Enzymes secreted through ruffled border into extracellular compartment.

- Transport of enzymes at apical pole involves MANNOSE-6-PHOSPHATE RECEPTORS.

4 Sections of Osteoclasts
1) On side of cell away from resorption cavity.
2) Contains nuclei and organelles.

1) Part of cell adjacent to resorbing bone.
2) Mitochondria and rough ER are prominent in cytoplasm near ruffled border.

1) Surrounds periphery of ruffled border.
2) Lacks organelles.
3) Contains actin and integrins which facilitates attachment of cell membrane to bone surface.

1) Lies btw basal zone and ruffled border.
2) Contains numerous endocytic and exocytic vesicles with hydolytic enzymes.
Subosteoclastic Compartment
- Small, circumscribed region btw osteoclast cell membrane and adjacent bone.

- Walls are the bone surface and the osteoclast cell membrane.

- Sealed off by CLEAR ZONE - attaches to bone surface around margins of the compartment.

- Osteoclast produces acid and hydrolytic enzymes which break down bone.

- Chemical reactions enclosed in compartment.

- Ruffled border projects into compartment.

- Considered functionally equivalent to a SECONDARY LYSOSOME.
Process of Bone Resorption
1) CO2 + H2O --> H2CO3 --> H+ + HCO3-

2) H+ pumped through cell membrane into subosteoclastic compartment - reducing pH.

3) Inorganic bone broken down w/i acidic extracellular compartment - crystals transported to adjacent capillaries.

*Organic phase (collagen) broken down by hydrolytic enzymes and collagenase (from osteoclast).

4) Then endocytosed and broken down to amino acids and monosaccharides and transferred to capillaries.

- HYDROXYPROLINE and N-TERMINAL COLLAGEN PEPTIDES in urine measures bone breakdown.
Regulators of Bone Resorption
-Vitamin D
*All activity of these factors mediated by OSTEOBLASTS which release osteoclast stimulating factor

-Osteoclasts have receptors for calcitonin but probably not for PTH

Organic Matrix
- Main component is TYPE I collagen.

- Collagen represents about 90% of organic bone content and is responsible for high tensile strength.

- Orientation determines lamellar or non-lamellar.

- Amorphous (non-collagenous) ground substance is LESS sulfated than that of cartilage.

- Proteoglycan molecules contain some GAGs which are linked by hyaluronic acid to form aggregates.

- Numerous non-collagen glycoproteins in bone matrix (i.e. osteocalcin, osteopontin, bone sialoprotein).
-part of organic matrix

-narrow seam of premineralized (uncalcified) matrix covering surface of mineralized bone

-12-15 day lag time btw formation of organic matrix and its mineralization

-adjacent to secretory ends of osteoblasts

-composed of ground substance and collagen fibers

Inorganic Matrix
-65% of dry weight of bone

- Consists of calcium phosphate arranged in apatite pattern

-"UNIT CELL" - the least number of Ca, PO4 and OH able to create ionic relationships
- Stacked together to form lattice of a crystal
- Aggregates form needles, blocks, or plates
- Hexagonal in shape

- Hydration shell surrounds each crystal
- Crystal has 3 surfaces: crystal interior, crystal surface, hydration shell

Mechanisms involved in precipitation of inorganic ions
- Inorganic ions are transported into osteoid from capillaries in connective tissue either btw or through osteoblasts.

- Precipitation of ions - at least 1 condition occuring
1) Homogeneous nucleation - high concentration of inorganic ions allowing initiation of crystalline formation.
2) Heterogenous nucleation - nucleating substance lowers energy barrier for precip. in absence of increase in ion concentration.
3) Inhibitors to mineralization must be inactive

- Increase in crystal dimension due to: addition of ions to crystals AND aggregates of crystals.

Matrix Vesicles
- Spherical, membrane-limited structures.

- Arise from budding off surface of osteoblasts and enter osteoid.

- Only seen in initial phase of mineralization.

- Possess cell membrane calcium pumps which pump into the vesicles: Ca2+, Ca-binding lipids, substances which destroy calcification-inhibitors, and alkaline phosphatase.

- Site of first apatite crystallite.
- Crystallite enlarges and ruptures vesicle.
- Adjacent crystallites fuse.
- Rapid growth of crystal-independent of matrix vesicles.

- Mineralization occurs in close relationship to collagen (during formation of collagen-based calcified tissues).

- Initially, crystallites form in "holes" or gap zones btw. tropocollagen molecules w/i collagen microfibrils.

Alkaline Phosphatase
- Group of enzymes important in mineralization.

- Serum concentrations reflect rates of bone formation.

- Identified in blood vessels, osteoblast cell membranes and osteoid.

- Enzymes provide phophate ions by hydrolyzing them from organic radicals at alkaline pH.

Other factors
BONE SIALOPROTEIN - nucletor in heterogenous nucleation


VITAMIN D - assists intestinal absorption of Ca and P and maintains their concentration in serum
-enhances synthesis of Ca bnding proteins in osteoid

-HORMONES (PTH, GH, calcitonin, estrogen) for bone metabolism

Lamellar vs. Non-lamellar
- Collagen fibers are oriented in a regular manner.
- Parallel w/i a lamella, different directions in adjacent lamellae (layers seen).
- Lacunae btw adjacent lamellae joined by multiple, narrow channels --> canaliculi.

- No layers seen b/c collagen fibers are randomly arranged.
- Lacunae connected by canaliculi.
- Most non-lamellar bone is replaced by lamellar.

Compact Bone
- AKA: DENSE BONE - composed of solid blocks of osseous tissue w/ small amt of soft CT.

- Occupies cortical regions of bone, surround cancellous bone

*LAMELLAR - organized into osteons, interstitial lamellae, and circumferential lamellae. Osteons have central Haversian Canal surrounded by concentric lamellae.

NON-LAMELLAR - in prenatal bones.
- Occurs in skull flat bone and tendon attachments to bone.
- At sites of fracture repair.
Types of Lamellae in Compact Bone
1) Interstitial Lamellae - partially resorbed osteons

2) Circumferential Lamellae - continuous layers on outer and inner surface of compact bone
-outer --> adjacent to periosteum (contains osteoprogenitor cells)
-inner --> adjacent to endosteum (narrower)

*Volkmann canals - arise from periosteum and endosteum. Carry blood vessels from peri. and end. to those in Haversian canals. Perpen. to long axis of osteons.

Cancellous (spongy) Bone
-contains soft marrow tissue btw. slender irregularly-shaped bars or trabeculae of mineralized bone matrix

-surrounded by thin layer of cortical bone

-trabeculae may be non-lamellar (primary) or lamellar (mature)
The mandible
exemplifies relationship between compact and cancellous bone

-compact bone --> covers body (ramus and alveolar process)
-cancellous bone --> forms trabecular network

-alveolar process
-outer plate - continuous with cortical bone on buccal and lingual aspects of body
-inner plate - surround tooth root and collagen fibers of periodontal ligament

AKA: alveolar bone proper, cribiform plate, lamina dura
Membrane bone formation
- Arises from mesenchyme w/o intervening cartilaginous model (ex. flat bones of skull, maxilla, and most of mandible)

1) Cells w/i foci of mesnechyme proliferate rapidly to produce dense cellular region

2) Cells enlarge and develop basophilic cytoplasm (due to ER), now with osteoblasts

3) Osteoblasts secrete osteoid (denser than mesenchyme b/c more collagen fibers; composed of ground substance and collagen fibers) and form rim around eosinophilic material.

4) Calcification occurs in middle of osteoid surrounded by non-Ca2+ eosinophilic osteoid

5) Calcifying tissue enlarges, some osteoblasts become trapped and form osteocytes

6) OSSEOUS SPICULES enlarge by appositional growth as osteoid deposited on surface by osteoblasts which continue to differentiate from adjacent mesenchyme.
Endochondral Ossification

1) occurs w/i a small cartilage model which roughly resembles the shape of the future bone (has EPIPHYSES and DIAPHYSIS). Diaphysis surrounded by a perichondrium
Endochondral Ossification

- Perichondrium becomes periosteum and deposits a layer of membrane bone on surface of cartilage model in MID-DIAPHYSIS - length to encircle entire diaphysis. Trabeculae widens, cancellous becomes compact

- Once membrane bone certain thickness, addition of bone on outer surface = resorption on internal surface

- Subperiosteal collar - inc. width of diaphysis and supports diaphysis during growth.
Endochondral Ossification

-changes begin to occur in the PRIMARY OSSIFICATION CENTER (center of diaphysis)
- Occur at same time of subperiosteal bone deposition
- Chondroblasts undergo hypertrophy w/i lacunae

*Chondroblasts and lacunae enlarge b/c cartilage matrix is reduced btw. adjacent enlarged lacunae

*residual cartilage matrix undergoes calcification

*hypertrophied chondrocytes - cut off from vascular supply -- NECTROTIC
Endochondral Ossification

blood vessels from surrounding periosteum erode and invaide the PRIMARY OSSIFICATION CENTER (necrotic chondrocytes and bars of calcified cartilage matrix)

-invasion creates MARROW CAVITY in center of diaphysis

-osteiod and thin layer of bone are deposited around each bar of calicified cartilage matrix

-expand central marrow cavity - osteoclasts resorb spicules of calcified cartilage, osteoid and bone

-2 region of ossification --> formation of bars and bone each end of medullary cavity
Endochondral Ossification

-up to this point --> rows of proliferating and calcifying cartilage, osteoid and bone known as METAPHYSEAL COLUMNS

-columns produces bone that is rapidly resorbed
-2 consequences
1)proliferation of cartilage in epiphysela ends forces epiphyses away from each other and elongates the diaphysis
2)expansion of central marrow cavity

*bone surrounding shaft derived from SUBPERIOSTEAL MEMBRANE BONE FORMATION
Endochondral Ossification

STEP 6 - SECONDARY OSSIFICATION CENTERS appear in center of each epiphyses - epiphyses enlarge in all directions

STEP 7 - EPIPHYSEAL DISC - cartilage btw. metaphysis and epiphysis
-growth of diaphyseal aspect = metaphyseal columns
-radial growth of epiphysis = cartilage on epiphyseal surface
Endochondral Ossification

STEP 8 - completion of lengtheing of diaphysis and disappearance of epiphyseal discs (long bone CANNOT increase in length)

STEP 9 - SUBPERIOSTEAL BONE encircling the diaphysis is formed from mesenchyme
-primary, non-lamellar bone widens trabeculae and forms compact, lamellar bone

STEP 10 - cartilage covering epiphysis persists as ARTICULAR CARTILAGE
Bone Remodeling
-first formed is non-lamellar

-primary, cancellous becomes compact at sites where trabeculae thicken at expense of soft marrow tissue btw trabeculae

-compact non-lamellar bone is resorbed and first replaced by tunnels of vascular CT which burrow through primary bone (ABSORPTION CAVITIES)

-layer of osteoid deposited on internal surface of residual bone

-osteoid mineralizes and first layers of mature lamellar bone is formed

-concentric layers of lamellar osteoid result in narrowing of vascular CT tunnel and formation of an OSTEON
-residual CT in center of tunnel becomes a Haversian canal

Early repair
-NEUTROPHILS enter the area and then MACROPHAGES, which remove extravasated red cells, fibrin, and necrotic tissue

-removal of clot by phagocytosis

-PROCALLUS = capillaries and fibroblasts from surrounding CT form granulation tissue

-CALLUS bridges the gap between fragments

- External callus forms around each other two broken ends on exterior

-Internal callus forms btw cortical and medullary surface of 2 fragments
Internal Callus
-clot invaded by osteoprogenitor cells of endosteum and multipotential cells of bone marrow

1)new bone TRABECULAE in medullary cavity from osteogenic cells of endosteum and marrow -- trabeculae interconnect fragments

2) new bone TRABECULAE btw ends of cortical bone
External Callus
-produced by periosteal activity with 3 zones

1) closest to outer surface of bone fragment. Osteogenic cells deposit bone matrix (membrane bone formation)

2) intermediate zone is immediately outside the osseous layer. Osteogenic cells in a less vascular environment become chondroblasts and form cartilage. Rest of callus is AVASCULAR

3) Surface zone is a proliferating osteogenic layer

**Callus is now fusiform mass of cancellous bone
Callus remodeling
-cartilage in external callus is replaced by bone via ENDOCHONDRAL OSSIFICATION

-dead bone is resorbed by osteoclats and replaced by cancellous bone --> replaced by dense cortical bone

-supplementary supporting trabeculae are resorbed