Normal Bone (Lecture 3.1, BB Bone, Lecture 2.1)
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Common Features of Bone and Cartilage
o (1) Provide support for body & allow certain amount of movement
 Requires strength & flexibility
o (2) Common origin from primitive mesenchymal cells
 That has not differentiated into a variety of matrue CT tissue types.
o (3) Contain cellular elements and extracellular matrix (ground substance and
fibrous tissue)
o (4) properties of particular tissue type (e.g. bone vs hyaline cartilage vs tendon)
depend on proportions of these elements (cells,matrix, type of cells and matrix)
Functions of bones determine histologic/gross appearance of bone
o (1) Mineral storage of Ca, Phosphate, poisons
o (2) Hematopoesis – produce blood cells at medullary canal
o (3) Mechanical support
 Lever framework for muscles and protection of soft tissues
 Wolffs law: bone remodels and forms according to biomechanical stress
put upon it.
 Osteoblasts and osteoclasts respond to changes in piezoelectric
currents induced by pressure upon bone by increase/decrease
bone formation
Bone constituents
o (1) Organic Matrix-protein: Collagen
 Gives bone resiliency to withstand tension/compression
o (2) Inorganic Minerals: Calcium salts
 Give bone strength and hardness!
o (3) Cells: make above, maintain, remodel (resorb/renew) matrix.
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Specific components
o (1) Extracellular Matrix: Type I collagen fibers laid down in a ground substance
(proteoglycans, etc.) - in bone, this is called OSTEOID.
 ground substance controls water and formation of collagen fibers
o (2) inorganic mineral salts
 deposited on these collagen fibers into hole zones
 Alkaline phosphatase creates alkaline environment around osteoblasts
that is favorable for calcium deposition  Calcium to settle to form
hydroxyapatite - Ca10(PO4)6(OH)2, which are these inorganic mineral
salts
o (3) cells
 osteoblasts - mononuclear cells derived from mesenchyme
 have eccentric nuclei with perinuclear clearing (Golgi zone)
 make collagen Type I and glycosaminoglycans to form
extracellular matrix (osteoid), which is non-mineralized matrix
 contain and secrete alkaline phosphatase
 have parathyroid hormone (PTH) receptors on surface
o Low dose of PTH stimulate osteoblasts -> bone formation
 osteocytes
 Osteoblasts buried in bone matrix (sit in lacunae) becomes
osteocytes
 Control local and phosphate level
 osteoclasts - multinucleated giant cells, derived from monocytes
 located in bone trabecular surface (Howship's lacunae)
 secrete acid phosphatase and proteases
 have "ruffled border" = microvilli which secrete acids which
dissolve mineral component of bone and lysosomal proteins
which resorb the organic matrix  remove mineralized bone
 Hormones
 Continuous PTH -> osteoblasts express RANKL or M-CSF->
osteoclasts have RANK (receptor) that binds to RANKL of
osteoblasts -> Increase osteoclast activity -> bone resorption > increase SCa
 Calcitonin is secreted by parafollicular cells of thyroid gland 
binds to G receptors of osteoclasts  decrease osteoclast
activity, dec bone resorption, dec SCa
Bone tissue type
o First type of bone formed by osteoblasts: Woven bone (aka primary, immature)
 Rapidly laid down  disorganized collagen fibers
 Weaker
 found in fetus, in abnormal states (tumor, reactive, adult fractures, etc.),
children at growth plate (osteoblasts laying down woven bone)
o Woven bone is then remodeled into Lamellar bone
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 Slowly produced, highly organized
 Strong, less flexible than woven bone
 Collagen is laid down in parallel layers or lamellae
 osteocytes are less numerous, evenly distributed throughout matrix
 is mature bone found in adult tissues and after development is finished
Bone strength:
o Cortical bone - is lamellar bone forming the hard, exterior shell
 Unit is the osteon, with central Haversian canal containing vessels, and
concentric lamella of bone
 Osteon connected to outer and inner cortical layers by Volkman's canals
o trabecular bone - also called "spongy bone"
 soft flexible, found at long ends of bone, trabeculate (a lot of SA)
 is site of most of metabolic activity of bone
Gross anatomy of bone
o (1) epiphysis, metaphysis (tumor prone), and diaphysis
o (2) physis - the growth plate - defines boundary between epiphysis and
metaphysis in the growing bone - accounts for lengthening of bone
Bone membranes
o Periosteum
 Nutrient foramina: Where blood vessels go through osteum and
periosteum
 fibrovascular sheath around cortex of bone
 insertion point for ligaments, tendons, muscles
 gives rise to some progenitor cells, such as the osteoblast, fibroblast,
chondroblast
 aids in fracture healing
o Sharpey’s fibers: collagenous fibers that extend off periosteum and go right into
bone: hole periosteum and bone together? important because when muscle
attach to it (tendon), it adheres to periosteum, which adheres to bone bc of
sharpeys.
o Endosteum: Internal surface of bone, containing osteoblasts/osteoclasts
o Osteon has Haversian canals and Volkmans’ canals (perpendicular)
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Bone Formation
o 1. enchondral ossification - most bones of body except: skull, part of clavicle
 Occurs during embryogenesis
 Secreted by chondroblasts and chondrocytes
 Cartilage “mold” of bone forms (anlagen) --> Mold grows→ chondrocytes
die --> Osteoblasts come in from blood to turn mold into bone
 Cartilage "mold" becomes bone in 2 places:
 (1) At center (diaphysis) of bone
 “Primary center of ossification”: Osteoblasts lay down matrix
(“ossification”)
 (2) At both ends (epiphysis)
 “Secondary centers of ossification”: Osteoblasts also lay down
matrix
 (3) These two centers grow towards each other (primary grows faster
than secondary)
 (4) Eventually anlagen (cartilage) trapped in the middle, forming
epiphyseal (growth) plate
 Plate found at ends of long bones between metaphysic and epiphysis
 Contains hyaline cartilage
o Have chondrocytes that grow toward epiphysis (ends)
o Have osteoblasts that lay down matrix (Growth) toward
diaphysis (center)
 Thus, as child grows, bone grows while having matrix being laid down
toward center of bone
 Growth plate “closes” at puberty, forming epiphyseal line
o 2. (intra)membranous bone formation - only in flat bones of skull
 osteoid (matrix) forms directly out of primitive mesenchyme/fibrous
tissue
 not from cartilage - an example of interstitial growth
 Osteoblasts lay down woven bone -> later remodel into lamellar bone
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Normal Bone Formation
o Intramembranous ossification (In utero and continues in adolescence) in which
compact/spongy bone forms from mesenchymal connective tissue. Flat bones of
face/skull/clavicles via this.
 1) Mesenchymal cells differentiate into specialized cells (e.g., capillaries,
osteoblastcs)
 2) Early osteoblasts appear in clust in ossification center and secrete
osteoid, uncalcified matrix, which hardens/calcify in few days, thereby
trapping osteoblasts within  osteoblasts become osteocytes; other
osteogenic cells differentiate into osteoblasts.
 3) Osteoid secreted around capillaries results in trabecular matrix, while
osteoblasts on surface of spongy bone become periosteum
 4) Trabecular bone near capillaries condense it into red marrow.
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o Endochondral ossification – bone forms from replacing hyaline cartilage
 Most bones (long bones) except skull and clavicles
 Long bone - 6-8 weeks after conception:
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Endochondral ossification follows five steps. (a) Mesenchymal cells
differentiate into chondrocytes. (b) The cartilage model of the
future bony skeleton and the perichondrium form. (c) Capillaries
penetrate cartilage. Perichondrium transforms into periosteum.
Periosteal collar develops. Primary ossification center develops. (d)
Cartilage and chondrocytes continue to grow at ends of the bone.
(e) secondary ossification centers develop. (f) Cartilage remains at
epiphyseal (growth) plate and at joint surface as articular
cartilage.
o Bones continue to grow in length until early adulthood. Growth stops when
chondrocytes stop proliferating and all that remains of plate is epiphyseal line.
 Epiphyseal (growth) plate of long bone is a layer of hyaline cartilage
where ossification occurs. On diaphyseal side, cartilage is ossified and
diaphysis grows in lenth.
 Proliferative zone: new chondrocytes via mitosis
 Maturation/hypertrophy zone
 Calcified matrix zone: cell death
o Bones also grow in diameter (both diaphysis, medullary cavity) simultaneously.
Modeling.
 Osteoclastds lines medullar cavity
 Osteoblasts (via intramembranous ossification) produce new bone
beneather periosteum
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