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Osteoclasts
Very large, motile cells with multiple nuclei which are essential for
matrix resorption during bone growth and remodelling
Large size and multinucleated condition are due to origin from fusion
of bone marrow-derived monocytes.
Development requires two polypeptides produced by osteoblasts:
macrophage-colony-stimulating factor (M-CSF) and the receptor
activator of nuclear factor-kB ligand (RANKL).
In areas undergoing resorption, osteoclasts on bone surface lie within
resorption lacunae (cavities in the matrix)
In active osteoblast membrane domain that contacts the bone forms
a circular sealing zone which binds tightly to bone matrix and
surrounds ruffled border (area with many surface projections).
Circumferential sealing zone allows formations of specialised
microenvironment between osteoclast and the matrix in which bone
resorption occurs.
Osteoclast pumps protons into subcellular pocket to acidify and
promote dissolution of adjacent hydroxyapatite, and releases matrix
metalloproteinases and other hydrolytic enzymes from lysosome-
related secretory vesicles for localised digestion of matrix proteins.
Activity is controlled by local signalling factors from other bone cells
Osteoblasts activated by parathyroid hormone produce M-CSF,
RANKL, and other factors that regulate the formation and activity of
osteoclasts.
Bone Matrix
50% of dry weight of bone matrix is inorganic materials – calcium
hydroxyapatite is most abundant. Bicarbonate, citrate, magnesium,
potassium, and sodium ions are found. Non-crystalline calcium
phosphate is also found.
Surface of hydroxyapatite crystals are hydrated, facilitating exchange of
ions between mineral and body fluids
Organic matter embedded in matrix I 90% type I collagen. Also includes
small proteoglycans and multi-adhesive glycoproteins such as
osteonectin
Calcium binding proteins and phosphatases released from cells in matrix
vesicles promote calcification of matrix.
Association of minerals with collagen fibres during calcification provides
the hardness and resistance required for bone function.
Decalcified bone matrix is acidophilic (due to high collagen content)
Periosteum
Periosteum covers external surface of bone.
Organised similar to perichondrium of cartilage, with outer fibrous layer
of dense connective tissue, containing bundled type I collagen,
fibroblasts and blood vessels.
Perforating (Sharpey) Fibres (bundles of periosteal collagen), bind
periosteum to the bone
Periosteal blood vessels branch and penetrate bone carrying metabolites
to and from bone cells
Inner layer is more cellular and includes osteoblasts, bone lining cells,
and mesenchymal stem cells called osteoprogenitor cells. Have potential
to proliferate extensively and produce new osteoblasts.
Endosteum
Covers internal surfaces of bones
Covers small trabeculae of bone matrix that project into marrow
cavities.
Contains osteoprogenitor cells, osteoblasts, and bone lining cells within
sparse, delicate matrix of collagen fibres.
Types of Bone
Type of Bone Histological Major Locations Synonyms
Features
Woven Bone, Irregular and Developing and Immature bone;
newly calcified random growing bones; primary bone;
arrangement of hard callus of bone bundle bone
cells and collagen; fractures
lightly calcified
Lamellar Bone, Parallel bundles of All normal regions Mature bone;
remodelled from collagen in thin of adult bone secondary bone
woven bone layers (lamellae),
with regularly
spaced cells
between; heavily
calcified
Compact bone, Parallel lamellae or Thick outer region Cortical Bone
80% of all lamellar densely packed (beneath
bone mass osteon, with periosteum) of
interstitial lamellae bones
Cancellous bone, Interconnected Inner regions of Spongy bone;
20% of all lamellar thin spicules or bones, adjacent to trabecula bone;
bone mass trabeculae covered marrow cavities medullary bone
by endosteum
Woven Bone
Non-lamellar and characterised by random disposition of type I collagen
fibres and is the first bone tissue to appear in embryonic development
and in fracture repair.
Usually temporary and is replaced in adults by lamellar bone, except in
few places in the body e.g. sutures of calvaria and in insertions of some
tendons.
Has a lower mineral content and a higher proportion of osteocytes than
mature lamellar bone.
These features reflect that immature woven bone forms more quickly
but has less strength than lamellar bone
Osteogenesis
Occurs by one of two processes:
Intramembranous ossification
Osteoblasts differentiate directly from mesenchyme and begin secreting
osteoid.
Bone formation within condensed mesenchyme bone formation begins
in ossification centres, areas in which osteoprogenitor cells arise,
proliferate, and form incomplete layers of osteoblasts around a network
of developing capillaries.
Osteoid secreted by osteoblasts calcifies forming small irregular areas of
woven bone with osteocytes in lacunae and canaliculi.
Continued matrix secretion and calcification enlarges these areas and
leads to fusion of neighbouring ossification centres
Anatomical bone forma gradually as woven bone matrix is replaced by
compact bone that encloses a region of cancellous bone with marrow
and larger blood vessels.
Mesenchymal regions that do not undergo ossification give rise to
endosteum and periosteum of new bone
Endochondral Ossification
Pre-existing matrix of hyaline cartilage is eroded and invaded by
osteoblasts, which then begin osteoid production
Forms most bones of the body and is especially well studied in
developing long bones where it consists of sequence of events.
Perichondrium becomes vascularised
Blood vessels supply new nutrients to mesenchymal cells which
differentiate and form osteoblasts.
Osteoblasts gather at diaphysis wall and form bone collar.
Chondrocytes in central cavity enlarge causing the matrix to calcify.
Matrix is now impermeable which causes cell death
Central clearing forms where cells have died and is supported by bone
collar
Healthy chondrocytes elsewhere cause elongation
Periosteal bud (contains artery, vein, lymphatics, and nerves) invades
cavity causing formation of spongy and delivers osteoblast and
osteoclasts
Bone continues to elongate
Primary ossification centre continues to enlarge
Osteoclasts break down newly formed spongy bone
Medullary cavity begins to form
Cartilage is then only deposited in epiphyses
Bony epiphyseal surface begins to form
Secondary ossification centre appears after birth at the epiphyses
Usually 2 in larger bone
Articular cartilage on surface protect and lubricates joints.
epiphyseal cartilage which connects each epiphysis to the diaphysis and
allows longitudinal bone growth