Lecture 3: Bone (Wronski) Flashcards
what creates the extreme hardness of bone?
mineralization of its extracellular matrix
name 4 functions of bone
- provides support and protection for the bodys soft tissue and organs
- serves as an attachment for muscle and tendons
- serves as a source of minerals (calcium and phosphate) for homeostasis
- encloses hematopoietic tissues (bone marrow)
what type of bone is very dense?
compact or cortical bone
what type of bone is less dense and lattice-like, and is composed of spicules and trabeculae of bone within bone marrow?
cancellous, trabecular or spongy bone (they all mean the same thing)
most bones possess what 5 features?
- articular surface
- cortex
- medullary cavity
- periosteum
- endosteum
define periosteum
specialized connective tissue that lines the external surface of cortical bone
what are the two layers of periosteum?
- outer fibrous layer
2. inner osteogenic (cambian) layer
is periosteum vascularized?
yes, very vascularized
what makes up the inner osteogenic layer of the periosteum?
osteogenic (osteoprogenitor) cells, stem cells capable of producing osteoblasts when needed for growth, maintenance, repair of bone
describe the endosteum layer of bone
it lines all internal surfaces of bone including the inner surface of cortical bone as well as the canals of cortical bone
define lamellar bone
the extracellular matrix that makes up one is organized into arrays of lamellae which is where the term lamellar bone comes from
define lacunae
numerous small cavities at the margins of each lamina. they each house an osteocyte
define canaliculi
minute canals that radiate out in all directions from each lacuna and communicate directly with neighboring lacuna.
how do osteocytes make cell-to-cell contact?
through specialized gap junctions
what are the 4 lamellar patterns of bone?
- cylindrical lamellae aka Haversian aka osteonal
- interstitial
- outer circumferential
- inner circumferential
define interstitial lamellae
angular lamellae situated betwen haversian systems
define inner and outer circumerferential lamellae
cortical lamellae that extend completely around the entire cortex just beneath the periosteum and endosteum
what is the difference between outer and inner circumferential lamellae?
the outer circumferential is along the periosteal surface, the inner circumferential is along the endocortical surface
define cement lines
thin lines of uncalcified matrix that delineatemargins of haversian and interstitial systems
define cylindrical lamellae aka haversian canals aka osteons
cylindrical lamellae of bone matrix that form the cylindrical units of bone that comprise haversian systems or osteons.
is bone vascular?
YES!
what are the central openings of haversian systems called? what do they contain?
haversian canals. they contain 1-2 small vessels they are usually either capillaries or postcapillary venules.
there are two vascular channels that communicate with haversian canals - what are they called?
- Volkmann’s canals aka communicating canals
2. perforating canals
in what direction do volkmann’s canals or communicating canals travel?
they pass transversely or obliquely through the lamellae
in what direction do the perforating canals travel?
they penetrate lamellae from the periosteum and endosteum to connect with haversian canals
what is the composition of the bone extracellular matrix in terms of organic material and inorganic material?
it is comprised of 1/3 organic matrix and 2/3 inorganic salts
what are the 3 main components of bone matrix?
- amorphous ground substance
- collagen fibers (TYPE 1)
- minerals
define amorphous ground substance
its principal components are proteoglycan aggregates composed of 3 things:
- chondroitin sulfate
- keratin sulfate
- hyaluronic acid (which is cartilage!)
what are bone specific proteins of the matrix? (this is within amorphous ground substance)
osteocalcin - protein bound to hydroxyapatite (this can be measured in blood)
osteopontin - cell binding protein that binds to hydroxyaptite
they are both made by osteoblasts
what is significant about type I collagen in bone matrix?
they are the principal organic component of the extracellular matrix and form templates for the mineralization of bone. in lamellar bone, it is highly ordered.
how are collagen fibers organized? what is significant about this organization?
in parallel arrays in each lamina of an osteon. it provides tensile strength to bone and resistance to shearing forces
what is the main mineral of bone?
a crystalline form of calcium phosphate called hydoxyapatite crystals
what is significant about the mineral content of bone?
the crystaline form called hydroxyapatite is responsible for the great compressive strength of bone
where do the hydroxyapatite crystals reside within the bone?
within the gap regions of collagen fibers
what are some of the anions present in bone?
carbonate, citrate, fluoride
what are some of the cations present in bone?
magnesium, lead, strontium and radium
what is a characteristic of demineralized bone?
very resilient and pliable with great tensile strength (you could tie a knot with a long bone!)
what is a characteristic of digested bones?
they retain hardness but become extremely brittle
there are 4 distinct cell types in bone. what are they?
- bone lining cells
- osteoblasts
- ostocytes
- osteoclasts
what is the morphology of bone lining cells and what is their function?
morphology: flattened cells that cover resting bone surfaces
function: involved in regulation of the flow of calcium ions from bone to the extracellular fluid
how do bone lining cells communicate with osteocytes?
cell processes within canaliculi
what do bone lining cells convert into and how?
they convert into osteoblasts via hormonal and mechanical stimuli
what is the morphology of osteoblasts?
usually ovid in shape and become flattened with age. they have a single eccentric nucleus and have basophilic cytoplasm with a prominent, pale staining Golgi apparatus next to the nucleus
what is the function of osteoblasts?
they form bone and are responsible for the production of TYPE 1 collagen, proteoglycans and bone specific proteins.
where are osteoblasts found? how do they communicate with each other?
- they are found in groups along bone surfaces
- they communicate via gap junctions
what is the uncalcified bone matrix laid down by osteoblasts referred to as?
osteoid
what is the thin line formed along the surface of bone lined by osteoblasts called?
osteoid seam
what happens to osteoblasts with the continued deposition of osteoid?
they eventually become surrounded by bone matrix and become osteocytes within lacunae and causes the osteoid to become calcified.
how do osteocytes communicate?
via gap junctions between their cytoplasmic processes within canaliculi
what is the function of osteocytes?
they function to maintain the extracellular bone matrix and play a role in regulating bone formation
define calcification
the deposition of calcium salts and specifically the extracellular deposition of hydroxyapatite in osteoid.
how are hydroxyapetite crystals formed?
when the product of calcium and phosphorus ion concentrations reach a certain threshold, calcium phosphate precipitates out and undergoes a conversion to hydroxyapatite crystals
what are the two mechanisms that influence hydroxyapatite deposition:
- extracellular osteoid and calcifying cartilage contain matrix vesicles
- collagen fibers and their specific molecular spacing act as nucleation sites for the deposition of hydroxyapatite within the gap regions.
bone mineralization occurs in two phases. what are they?
- primary mineralization
2. secondary mineralization
what percentage of bone mineralization is primary vs. secondary?
primary is about 70 - 75% secondary is about 25 - 30%
what is the morphology of osteoclasts?
they are large, multi-nucleated cells that are irregularly-shaped with an acidophilic cytoplasm that has a foamy appearance due to the presence of many vacuoles
what is the main function of osteoclasts?
they resorb bone
where are osteoclasts located?
within depressions in the bone surface called Howship’s lacunae or resorption bays.
what hormones influence osteoclast activity and does it increase or decrease?
estrogen and calcitonin - decreases osteoclast activity
parathyroid hormone - increases osteoclast activity
what is the effect of resorption bays or lacunae on the appearance of bone?
it gives a scalloped appearance to bone surfaces actively undergoing resorption. the cell surface immediately opposite bone surfaces have a ruffled border created by numerous infoldings of the plasma membrane.
define sealing zone and what does it create? what is significant about it?
an intracellular actin ring that is created when the plasmalemma is closely applied to the bone surface. this ring creates an extracellular subosteoclastic compartment. this is the site of bone resorption
the resorption of bone involves what 2 processes?
- the decalcification of bone matrix
2. the digestion of collagen, proteoglycans and other organic components
define decalcification
the solubilization of calcium salts by acidification of the local subosteoclastic compartmental environment
what is required in order to initiate digestion of the organic components of bone matrix?
the release of lysosomal acid hydrolases (cathespins) in the subosteoclastic compartement by exocytosis
how is decalcification accomplished? there are 3 processes.
- the actions of carbonic anhydrase in the cytoplasm of the ruffled border to produce bicarbonate and hydrogen ions
- the active transport of hydrogen ions into the subosteoclastic compartment by an ATP-dependent proton pump present in the osteoclast plasmalemma of the ruffled border
- chloride ions pass into the subosteoclastic compartment through a chloride channel which results in a highly acidic environment
define modeling
bone formation and resorption occur at separate bone surfaces
where does bone formation occur?
at the periosteal surface
where does bone resorption occur?
at the endocortical surface
define drift
bone modeling will occasionally result in a change in position of bone in space
in what type of animals does bone modeling typically occurr?
young, growing animals
define remodeling
old bone is resorbed by osteoclasts and replaced by new bone deposited by osteoblasts at the same bone surface
which comes first - bone resorption or bone formation?
bone resorption always precedes bone formation
what factors initiate bone remodeling?
- hormonal signals
2. accumulation of microdamage (microcracks) in old bone
what is the sequence of events for bone remodeling?
- activation
- resorption
- formation
affectionately denoted as A-R-F
define activation.
first step of bone remodeling. it involves a stimulus that results in activation of osteoclasts at some point along the canal of an osteon.
define resorption
2nd step of bone remodeling. it involves the resorption of bone by osteoclasts along a portion of existing osteons to form a resorption cavity.
how do resorption cavities formed in the process of resorption of bone remodeling differ from osteonal canals?
resorption cavities differ from osteonal canals by having irregularly etched margins that are lined by osteoclasts
define formation
formation involves replacement of resorption cavities with new, concentric lamellar bone produced by osteoblasts. this process eventually replaces older osteons first formed during osteogenesis.
what do the outer limits of resorption and the initial site of new bone deposition contain? (this occurs in the process of formation in bone remodeling)
a thin layer of uncalcified bone matrix that forms the cement or reversal lines at the margins of osteons and interstitial lamellae.
the intrusion of newly formed osteons into regions of previous osteons results in what?
the formation of interstitial lamellae
bone remodeling is an important component of what?
the calcium homeostatic system
bone resorption is regulated mainly through what pathway?
the RANK/RANKL/OPG signaling pathway
define Receptor Activator of Nuclear factor-Kappa-B (RANK)
it is a cell surface receptor on osteoclasts (both precursor and mature)
what triggers osteoclasts to differentiate from osteoclast precursor cells to multi-nucleated? what else is triggered by the same action?
when a ligand for the RNAK receptor (RANKL) binds to RANK
this also triggers mature osteoclasts along bone surfaces to become activated
what has a strong stimulatory effect on bone resorption?
RANKL - because it is what activates osteoclasts
what secretes RANKL?
osteoblasts
what do osteoblasts secrete?
RANKL and osteoprotegrin (OPG)
what is osteoprotegerin (OPG)?
a decoy receptor with a high affinity for RANKL and is therefore an inhibitor of bone resorption
based on the two different receptors secreted by osteoblasts, what activity do they stimulate and/or inhibit?
osteoblasts can
- stimulate bone resorption via RANKL
- inhibit bone resorption via OPG
what is a key factor in the regulation of bone resorption and remodeling?
the balance between RANKL and OPG
what has been developed as a marker for bone resorption?
an assay for serum RANKL
what two cells communicate to regulate bone formation?
osteocytes and osteoblasts
what protein do osteocytes secrete to inhibit bone formation? what does that protein then bind to inhibit bone formation?
sclerostin - a protein that binds to the lipoprotein receptor-related protein 5 (LPR5) receptor on osteoblasts
