Endochondral Ossification, Bone Growth & Remodeling Flashcards
Endochondral Ossification
• Endochondral Bone Formation:
– Long bones: ____ and ____ skeleton.
– Replacement of a ____ template by bone.
axial
appendicular
hyaline cartilage
Endochondral Ossification: Primary Ossification Center
- formation of primary ossification center
differentiation of subpopulations of chondrocytes within the hyaline template: becoming ____ chondrocytes
induced to proliferate > they become hypertrophic (absorb liquid and enlarge) > a signal for a release of ____ that will induce the differentiation of the ____
the cells within the perichondrium will become ____ and will give rise to ____ > this area is now known as the ____
hypertrophic chondrocytes secrete VEGF > induces invasion of ____ [hyaline cartilage has no BV]; these new BV bring ____
hypertrophic
GF
perichondrium
OPC
osteoblasts
periosteal collar
vasculature
osteoblasts/clasts
Endochondral Ossification: The Growth Plate
reserve zone > cartilage located farthest away from the ____; not directly involved in the growth plate; consists of regular ____
proliferative zone > 2-3 division of chondrocytes > ____
growth plate
hyaline cartilage
isogenous groups
Endochondral Ossification: The Growth Plate
hypertrophic zone > chondrocytes absorb fluisds and expanded; matrix of cartilage has been ____; some ____ of this matrix takes place (difference bt mineralization and calcification)
vascular invasion zone > ____ invading the primary ossification center, carrying ____ > formation of bone within this zone due to the vasculature
condensed
calcification
blood vessels
OPC
Endochondral Ossification: The Proliferative Zone
chondrocytes are induced to proliferate; ____ growth (share the same ____)!!!
capable of cell division and remain associated > ____ (or ____)
interstitial
lacuna
isogenous groups
chondron
Endochondral Ossification: The Hypertrophy Zone
same number of cells as in ____ zone; the only way for the cells to enlarge is to squeeze the ____ matrixes thinner and thinner
you start seeing ____ in the lower part of the hypertrophy zone (not mineralization)
proliferative
interterritorial
calcification
Endochondral Ossification: The Hypertrophy Zone
interterritorial matrix has been squeezed into ____ (the matrix has already been calcified)
problem! in calcification > cannot ____ substances as effectively > the cells located in this zone are ____ > engage in ____
septa
diffuse
starving
apoptosis
Endochondral Ossification: Zone of Vascular Invasion
round, blue-stained structure > ____ cells/tissue
long dotted line enclosure: ____ left over from the hypertrophic cells
also see OPC; that attach themselves to the ____ matrix in order to start depositing bone
hematopoietic
septa
calcified
Endochondral Ossification: Zone of Vascular Invasion
also have the presence of ____ > dissolve away mineralized matrixes > already beginning the process of ____ > in order to eventually achieve a mature, non-primitive bone
the equilibrium of degradation/construction has already begun; but still in favor of the ____
osteoclasts
remodeling
osteoblasts
Bone Growth in Length: Osteoclastic “chase” and chondrocytic “run”
differentiation of chondrocytes takes place closer and closer to the ____ = osteoclastic “chase”
in order for bone to grow in length > must achieve an equilibrium; ____ must be dividing fast enough (interstitial growth; also appositional growth from the cells in the perichondrium……??????)
equilibrium > cartilage is expanding just as fast as the bone is growing;
if the ____ is too fast for the reserve zone to keep up with its own provision of chondrocytes > the bone cannot grow in length anymore > the bone will be ____
the same is true for the opposite scenario
diaphysis
reserve zone
VIZ (vascular invasion zone)
shorter
Endochondral Ossification: Secondary Ossification Centers
POC induces the invasion of the epiphysis > ____ AT A TIME > these are called secondary ossification centers
____ regulates the growth of SOC > regulating the growth process and the process of hypertrophy of the chondrocytes
upon complete formation of SOC > the growth plate is ____ to a very small area
even after completion of the SOC > there is still growth in ____ > however, all the zones are RESTRICTED to the small area surrounding the ____ > still capable of growing in length
____ > replaces the plate (looks like a suture)
step 4/5 takes place after ____; all the others steps take place in the ____
one
Ihh
condensed
length
metaphysis
epiphyseal line
puberty
embryo
Endochondral Ossification: Secondary Ossification Centers
SOC > ____ are apparent; surrounded by epi/endo > bringing OPC/osteoblasts that start depositing bone and osteoclasts that eliminate cartilage
capillaries
Endochondral Ossification: Key regulators of chondrocyte differentiation within the growth plate
- Ihh: Secreted by ____ chondrocytes. Stimulates synthesis of ____. Regulates formation of ____.
- PTHrP stimulates the proliferation of chondrocytes in the ____.
- PTHrP inhibits the differentiation of ____ chondrocytes into ____ chondrocytes.
- Hypertrophic chondrocytes secrete:
• ____, provides structural
support to cells.
• ____, inducer of vascular invasion.
high levels of Ihh > high PTHrP > slows down the rate of the ____ migrates upward > gives the bone more chances to grow in ____ (also increases amount of ____)
proliferative zone
PTHrP
bone collar
reserve zone
proliferative zone
hypertrophic
type X collagen
VEGF
VIZ
length
cartilage
Bone Growth: Bone Modeling
• ____: Alteration in the size and shape of bones during growth by the processes of bone formation and resorption:
- Growth in width of the ____ long bone cylinder and expansion of the interior ____ cavity.
- Shaping of the ends of the long bones to convert the broad ____ funnel into a narrow ____ cylinder.
- Enlargement of the ____ curvature.
• Bone growth is an ____ mechanism, in which new bone is added to an existing bone surface. Intersititial growth is ____ in a rigid calcified ECM.
modeling
diaphyseal marrow metaphyseal diaphyseal cranial vault
appositional
not possible
Bone Growth in Width
Take a look at the slides!
____ capillary becomes enclosed inside the bone
area on the ____ of the haversian canal will also grow in layers due to the influx of OPC/osteoblasts due to the capillary
formation of multiple ____ > thereby growing in width/diameter
periosteal
inside
haversian canals
Factors Affecting Bone Growth
• 20 or more hormones, vitamins and growth factors (____ to hormones) control bone growth.
• During infancy and childhood:
– Epiphyseal plate activity is stimulated by ____ (released by the ____ pituitary).
• During puberty:
– ____ and ____:
• ____ promote adolescent growth spurts by stimulating proliferation of osteogenic cells and
chondrocytes in growth plate.
• Cause masculinization and feminization of specific parts of the skeleton.
• Later induce epiphyseal plate ____, ending longitudinal bone growth.
– Adolescent women grow ____ than men and reach their full height ____ (____ has strong effect on bone growth).
– Adolescent males grow for a ____ time due to sustained high levels of ____ resulting in larger average stature.
- Growth ceases when the epiphysis & diaphysis ____ (epiphyseal plate “closure”): around age ____ for males and ____ for females.
- Anabolic steroids (but not ____) may cause ____ closure of growth plate producing short adult stature.
second
growth hormone
anterior
estrogen testosterone intially closure faster earlier estrogen longer testosterone
fuse 21 18 oral contraceptives premature
Bone Remodeling
• Remodeling: Occurs ____ life.
• New bone: converts woven bone into mature lamellar bone.
• Mature bone: continuous turnover of bone.
• In adults, ~____% of the cortical bone and ____% of trabecular bone is remodeled per
year. (____ years, all trabecular bone has been completely remodeled)
• Concerted action of osteoclasts and osteoblasts: ____.
throughout 3 25 4 bone remodeling unit (BRU)
Cortical Bone Remodeling
• Cortical bone BRU:
–____ at its leading edge (____) tunnel through the mineralized matrix.
–____ at its trailing edge (____) fill in the tunnel with concentric
bone lamellae.
–The center of the tunnel is occupied by the
penetrating ____, which is the
source of the osteoprogenitor cells.
• The process gives rise to the ____ structure.
Reverse from destruction to construction?
osteoclast cutting cone osteoblast closing cone blood vessel osteon
Trabecular Bone Remodeling
• In trabecular bone:
– The BRU is the ____ on the trabecular surface.
– Osteoblasts and osteoclasts derive from ____ in the marrow.
• Remodeling gives rise to lamellar bone, as filling of the resorption cavities takes place in layers by the surface osteoblasts.
howship’s lacuna
progenitor
Healing of Bone Fractures
1. Fracture hematoma: blood clot from broken blood vessels; swelling.
- Soft callus formation: collagen and fibrocartilage is formed by ____ and infiltrated by capillaries at site of break; ____ differentiate into chondrocytes.
- Callus ossification: soft callus replaced by hard woven bone callus in ~____ weeks; resembles the ____ process of ____ bone formation.
- Remodeling: woven bone is replaced by compact bone in ~____ months; excess bone is removed by osteoclasts.
fibroblasts
periosteal
six
embryonic
endochondral
six
Segmentation of the skeleton: Joints
Skeletal elements are separated from each other by the joints
- Types of joints (arthroses): – Non-synovial joints:
- Fibrous joints (____) : skeletal elements are directly linked by ____ tissue, e.g., sutures between skull bones, ribs and sternum. No ____.
- Cartilaginous joints (____): two skeletal elements are linked by ____, e.g., joints between vertebral bodies. ____ movement.
– Synovial joints (____) have a joint cavity enclosed by a fibrous capsule, lined by the ____ membrane. E.g. joints separating skeletal elements in limbs: ____ movement.
synovial membrane is ____; synovial fluid thereby is rich in nutrients > it is how the articular cartilage [no perichondrium] receives its nutrition
synarthroses fibrous movement amphiarthroses cartilage limited
diarthroses
synovial
free
vascularized
Synovial Joints
in place of future articulation; ____ is altered: they ____ differently than the rest of the condensation of mesenchyme > they differentiate, hypertrophy and then die via ____ > now have signaled to cartilage skeleton that there is not going to be any ____ ossification
condensation
differntiate
apoptosis
endochondral
