Block IV: Bone Flashcards
Bone is a specialized connective tissue characterized by a:
mineralized matrix
Whats typical of all connective tissues?
- Abundant extracellular matrix
- Isolated cells entrapped in matrix
- Vascular
What is atypical of connective tissues and specific of bone?
- The mineral in the matrix is calcium phosphate in the form of hydroxyapatite crystals.
- Many cells are polarized
- Many cells have junctional complexes
identify
Light micrograph of decalcified bone stained with H&E
What are the functions of bone?
- Support
- Protection (central nervous system, hemopoietic cells, organs)
- Storage site for calcium and phosphate. Homeostasis.
- Lever system (locomotor system)
What are the commonly used techniques to study bone?
To visualize organic components: decalcified
To visualize inorganic components: ground bone (undecalcified)
identify
decalcified bone
identify
ground bone (undecalcified)
What is the osteoid?
Organic component secreted first by osteoblasts, not mineralized yet
What disease of collagen type 1 causes brittle bones?
osteogenesis imperfecta
WHat is the gorund substance of bone composed of?
Proteoglycan aggregates
Multiadhesive glycoproteins
Bone-specific vitamin K- dependent proteins
Growth factors and cytokines
What are proteoglycan aggregates and its function?
Glycosaminoglycans (GAGs) (hyaluronan, chondroitin and keratan sulfates).
Contribute to the strength of bone, binding of growth factors and may inhibit mineralization.
What are Multiadhesive glycoproteins and its function?
osteonectin, osteopontin and sialoproteins.
In general mediate binding of cells and fibers to mineralized matrix
What are Bone-specific vitamin K- dependent proteins and its functions?
including osteocalcin, which captures calcium from the circulation and attracts and stimulates osteoclasts in bone remodeling; protein S, which assists in the removal of cells undergoing apoptosis; and matrix Gla-protein (MGP), which participates in the development of vascular calcifications.
What growth factors and cytokines are present in bone?
insulin-like growth factors (IGFs), tumor necrosis factor α (TNF-α), transforming growth factor β (TGF-β), platelet-derived growth factors (PDGFs), bone morphogenic proteins (BMPs), and interleukins (IL-1, IL-6).
What is the function on BMPs in bone?
BMPs induce the differentiation of mesenchymal cells into osteoblasts
WHat is recombinant human BMP-7 used for?
also known as osteogenic protein-1 (OP-1), is now used clinically to induce bone growth after bone surgery involving large bone defects, spinal fusions, or implantation of graft materials
What are lacunae and canaliculi?
Bone matrix contains lacunae connected by a network of canaliculi. The osteocyte extends numerous processes into small tunnels called canaliculi
osteocytes processed communicate through?
gap junctions
identify
Ground bone showing bone lacuna and bone canaliculi
Where are osteoprogenitor cells derived from?
derived from mesenchymal stem cells; they give rise to osteoblasts
WHat are osteoblasts?
cells that secrete the organic extracellular matrix called osteoid, when the cell is
surrounded with its secreted matrix, it is referred to as an osteocyte
what are osteocytes?
mature bone cells entrapped in matrix and housed in their own lacunae. They
have processes that extend through canaliculi and communicate via gap junctions with other osteocytes. Bone tissue depends on the osteocytes to maintain viability
what is bone-lining cells?
are cells that remain on the bone surface when there is no active growth.
They are derived from those osteoblasts and remain latent and some can give rise to osteoblasts
what are oseteoclasts?
bone-resorbing cells present on bone surfaces where bone is being removed or
remodeled (reorganized) or where bone has been damaged.
Are phagocytotic cells derived from cells in bone marrow that give rise to monocyte / macrophage progenitor cells
identify
Cells in Bone
Osteoblasts and osteocytes
Bone is made from?
bone tissue, connective tissue and hemopoietic tissue, fat, blood vessel and nerves.
How do you know if hyaline cartilage is present in bone?
If the bone forms a freely movable joint (synovial) then cartilage (hyaline) is also present
What is the compact or dense part of the bone?
layer forms the outside of the bone (compact bone)
What is the spongy or cancellous part of bone?
sponge-like meshwork consisting of trabeculae (thin, anastomosing spicules of bone tissue) forms the interior of the bone
full of bone marrow and blood vessels
identify
compact and spongy
Describe long bones
are longer in one dimension than other bones. Consist of a shaft and two ends (e.g., the tibia and the metacarpals).
Describe short bones
are nearly equal in length and diameter (e.g., the carpal bones of the hand).
describe flat bones
are thin and plate-like (e.g., the bones of the skull cap and the sternum). They consist of two layers of relatively thick compact bone with an intervening layer of spongy
bone
Describe irregular bones
have a shape that does not fit into any one of the three groups just described; the shape may be complex (e.g., a vertebra),
What is the periosteum?
Covers external surfaces of bones, consists of an outer fibrous layer that
resembles other dense connective tissues and an inner, more cellular layer that
contains the osteoprogenitor cells.
What is the endosteum?
Covers bone cavities, canals and trabecula. It has osteoprogenitor cells and bone-lining cells bone, called endosteal cells
How is the growth of bone tissue?
Appositional growth via
intramembranous ossification
in periosteum or endosteum
identify
Cross section of decalcified bone, displaying skeletal muscle (SM) fibers that will insert a short distance from this site. The
outer fibrous periosteum (FP) and the inner osteogenic periosteum (OP) are distinguishable due to the fibrous component
of the former and the cellularity of the latter. Note the presence of the inner circumferential (IC) lamellae, osteons (Os),
and interstitial lamellae (asterisk). Also observe the marrow (M) occupying the marrow cavity, as well as the endosteal
lining (arrow).
What are haversian systems?
structural units found in mature bone, also called osteons
What is the haversian canal?
The osteon consist of concentric lamellae surrounding a central canal (Harvesian canal) that contains vascular and nerve supply.
What si the inner and outer circumferential lamellae?
follow the entire inner and outer circumferences of the shaft of long bones
What is the interstitial lamellae?
are remnants of previous concentric lamellae
identify
Cross section of decalcified compact bone, displaying osteons or haversian canal systems (Os) as well as
interstitial lamellae (IL). Each osteon possesses a central haversian canal (HC), surrounded by several
lamellae (L) of bone. The boundary of each osteon is visible and is referred to as a cementing line
(arrowheads). Neighboring haversian canals are connected to each other by Volkmann’s canals (VC), through
which blood vessels of osteons are interconnected to each other
how can haversian canal and volkmans canal be reconstructed?
from compact bone
What is a woven bone?
immature bone, does not display an
organized lamellate appearance
how is woven bone also referred as?
as nonlamellar or bundle bone due ot the interlacing arrangement of the collagen fibers
how are cells in immature bone?
contains relatively more cells per unit area than does mature bone.
The cells in immature bone are randomly arranged.
how is th ematrix of immature bone?
more ground substance than the matrix of mature bone and stains more intensely with hematoxylin and in mature bone it stains more with eosin
Describe the osteoblast
is the differentiated boneforming cell. Retains the ability to divide.
what does the active bone deposition of the osteoblast do?
increases circulating levels tissue non specific alkaline phosphatase (TNAP) and osteocalcin, considered markers of osteoblastic activity [period of active growth]
Whst does osteoblast secrete?
It secretes both type I collagen (which constitutes 90% of the protein in bone) and
bone matrix proteins, which constitute the initial unmineralized bone called osteoid
What structure is responsible for the calcification of bone matrix?
the osteoblast
how many osteoblasts differentiate into osteocytes?
Only 10% to 20% of osteoblasts differentiate into osteocytes. Others remain inactive cells in periosteal or endosteal regions. The majority of osteoblasts undergo apoptosis
identify
osteoblast
Matrix vesicles are released from?
from the osteoblast at the osteoblast–osteoid interface.
What does the plasma membrane of matrix vesicles contain?
contains Ca2+ channels (annexins), Na+−phosphate cotransporters (NPT3), and
tissue nonspecific alkaline phosphatases (TNAP)
What happens in the mediated mineralization phase inside the matrix vesicle?
both Ca2+ and PO4 ions accumulate in the vesicle lumen and initiate a stepwise
process of hydroxyapatite crystals formation. These crystals emerge into the
extracellular matrix.
What happens in the mediated mineralization phase outside the matrix vesicle?
High concentrations of Ca2+, PO4 ions, and Ca2+-binding proteins provide a favorable environment for hydroxyapatite crystals growth
matrix vesicles expand into:
expand into spaces between
collagen fibrils and a wave of mineralization
sweeps through the osteoid
Where is the osteocyte located?
The osteocyte is enclosed by bone matrix, and occupies a space, or lacuna, that conforms to the shape of the cell.
osteocytes are enclosed by?
Osteocytes cytoplasmic processes are enclosed by the canaliculi within the matrix.
They communicate with other osteocytes and bone-lining cells by means of gap junctions formed by a family of bone-expressed connexins
osteocytes respond to?
mechanical forces applied to the bone. During reduced mechanical stress, the osteocytes respond by secreting matrix metalloproteinases (MMPs)
what is osteocytic osteolysis?
Degradation of bone by MMPs secreted by the resorptive osteocytes previously;
The current concept of osteocytic remodeling is that the osteocyte is responsible for calcium and phosphate ion homeostasis
identify
Scanning electron micrograph of an acid-etched, resin embedded
sample of bone from a 4-month-old mouse shows a network of
canaliculi interconnecting three osteocyte lacunae (OL) and
endosteal cells. In this method, resin fills the osteocyte lacunae,
canaliculi, osteoid, and bone marrow spaces but does not
penetrate mineralized bone matrix. Phosphoric acid is usually
used to remove the mineral, leaving behind a resin cast. The
upper part of the image is occupied by bone marrow cells (BM),
which are separated from bone tissue by the endosteum (EOS).
What are the stages of an osteocyte?
quiescent osteocyte- that contains only a few profiles of rER and a few mitochondria (M). The cell virtually fills the lacuna that it occupies; the arrows indicate where cytoplasmic processes extend into canaliculi. Hydroxyapatite crystals have
been lost from the matrix, which is ordinarily mineralized (MM), but some hydroxyapatite crystals fill the pericellular space. The dark band marking the boundary of the lacuna is the osmiophilic lamina (OL)
formative osteocyte- containing larger amounts of rER and a large Golgi apparatus (G). Of equal importance is the presence of a small amount of osteoid in the pericellular space within the lacuna. The osteoid shows profiles of collagen fibrils (arrows) not yet mineralized.
resorptive osteocyte- containing a substantial amount of rER, a large Golgi apparatus, mitochondria (M), and lysosomes (L). The pericellular space is devoid of collagen fibrils and may contain some flocculent material. The lacuna containing a resorptive
osteocyte is bounded by a less conspicuous osmiophilic lamina (OL).
identify
quiescent osteocyte
identify
formative osteocyte
identify
resorptive osteocyte
Bone-lining cells are derived from?
osteoblasts and cover bone that is not remodeling
what are periosteal cells?
bone-lining cells in the surfaces in the external bone
What are endosteal cells?
lining the internal bone surfaces
where are gap-junctions present in bone?
present where the bone-lining cell
processes contact one
another
What is the function of bone-lining cells?
maintenance and nutritional support of
the osteocytes
identify
bone-lining cells
The osteoclast is responsible for?
bone resorption
What happens as a result of the activation of osteoclasts?
a resorption bay (Howship’s lacuna) is
observed, directly under the cell.
What does osteoclast resorb do?
Osteoclast resorb bone tissue releasing
protons, hydrolytic enzymes and carbonic
anhydrase.
WHat does the acidic environment of the osteoclast do?
initiates the degradation of the mineral components (hydroxyapatites)
to calcium ions, inorganic phosphates and water.
identify
osteoclast
What structure is part of the mononuclear phagocytic system?
osteoclast derived from CFU-M homopoietic progenitor cells; large multinucleated cells with many lysosomes
Where are osteoclasts derived from?
fusion of granulocyte/monocyte progenitor cells (GMP, CFU-GM), which originate from multipotential common myeloid progenitor cells (CMP, CFU-GEMM.
what do stromal cells in bone marrow secrete?
monocyte colonystimulating factor (M-CSF), tumor necrosis factor (TNF), and several interleukins (ILs)
What does osteoclasts precursors express?
c-fos, NFκB, and receptor molecules called RANK (receptor activator of nuclear factor-
κB
What signaling is essential for osteoclast differentiation and maturation and by what can be blocked?
The signal generated by the interaction of the RANK receptor with the RANK ligand (RANKL) molecule
These pathways can be blocked by osteoprotegerin (OPG).
What happens to bone resorption during inflammation?
T lymphocytes produce both soluble and membrane-bound RANKL molecules, which
increase bone resorption
What regions are exhibited when osteoclast are actively resorbing bone?
Ruffled border-secretion of metalloproteinases
clear zone- actins and integrins sellan la region
basolateral region
Whta is released during the resorb of bone by osteoclast and the function
Osteoclast resorb bone tissue releasing protons, hydrolytic enzymes and
carbonic anhydrase. The acid environment initiates the degradation of the
mineral components (hydroxyapatites) to calcium ions, inorganic phosphates
and water.
What does the parathyroid hormone does?
Parathyroid hormone (PTH) secreted by the principal (chief) cells of the parathyroid
glands is the most important regulator of calcium and phosphate levels in the
extracellular fluid.
do osteoclasts have PTH receptors?
no; PTH exerts only an indirect effect on osteoclasts
What structures have PTH receptors?
osteocytes, osteoblasts, and T lymphocytes all have PTH receptors that activate adenyl cyclase, increasing intracellular levels of cAMP
what hormone suppresses RANKL production by T lymphocytes?
estrogen and **Osteoprotegerin (OPG) produced by osteoblasts also blocks the RANKL
how does brief exposure to PTH increases bone mass?
through the cyclic adenosine monophosphate (cAMP)/IGF-1 pathway in osteocytes and osteoblasts
What does calcitonin do?
secreted by the parafollicular cells of the thyroid gland, has the singular
effect of reducing osteoclastic activity
What is a market for osteoclast activity?
Tartrate-resistant acid phosphatase TRAP
What causes osteopetrosis?
Deficiency of cathepsin K, carbonic anhydrase II, and proteins encoding
the proton pump (TCIRG1),
What is osteoporosis?
congenital disease characterized by increased bone density and defective osteoclast
function.
what happens to the osteoclasts in individuals with osteoporosis?
osteoclasts do not function properly, which causes bones to appear dense on X-ray; however, bones are actually very fragile and break easily
identify
houseship lacunae osteoclast
identify
Scanning electron micrograph of trabecular bone. a. trabecular bone obtained from a vertebral body of a healthy individual. b. Same region from elderly woman showing extensive signs of osteoporosis
describe osteoporosis
- It is characterized by progressive loss of normal bone density accompanied by the
deterioration of its microarchitecture. - In healthy individuals, osteoclast activity is primarily regulated by PTH and to a lesser
degree by IL-1 and TNF - Estrogens (especially estradiol) inhibit formation of these cytokines, therefore limiting the activity of osteoclasts.
- There are three general types of osteoporosis:
**Type I primary osteoporosis occurs in postmenopausal women.
**Type II primary osteoporosis occurs in elderly individuals in their seventh or
eighth decade of life
***Secondary osteoporosis develops as a result of drug therapy (i.e.,
corticosteroids) or diseases that may affect bone remodeling,
malnutrition, weightlessness, hyperparathyroidism, metastatic cancers
