Endochondral Ossification, Bone Growth & Remodeling

Question 1

Endochondral Ossification

• Endochondral Bone Formation:
– Long bones: ____ and ____ skeleton.
– Replacement of a ____ template by bone.

Answer 1

axial
appendicular
hyaline cartilage

Question 2

Endochondral Ossification: Primary Ossification Center

1. 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 ____

Answer 2

hypertrophic
GF
perichondrium

OPC
osteoblasts
periosteal collar

vasculature
osteoblasts/clasts

Question 3

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 > ____

Answer 3

growth plate
hyaline cartilage

isogenous groups

Question 4

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

Answer 4

condensed
calcification

blood vessels
OPC

Question 5

Endochondral Ossification: The Proliferative Zone

chondrocytes are induced to proliferate; ____ growth (share the same ____)!!!

capable of cell division and remain associated > ____ (or ____)

Answer 5

interstitial
lacuna

isogenous groups
chondron

Question 6

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)

Answer 6

proliferative
interterritorial

calcification

Question 7

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 ____

Answer 7

septa

diffuse
starving
apoptosis

Question 8

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

Answer 8

hematopoietic
septa
calcified

Question 9

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 ____

Answer 9

osteoclasts
remodeling
osteoblasts

Question 10

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

Answer 10

diaphysis

reserve zone

VIZ (vascular invasion zone)
shorter

Question 11

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 ____

Answer 11

one
Ihh

condensed

length
metaphysis

epiphyseal line

puberty
embryo

Question 12

Endochondral Ossification: Secondary Ossification Centers

SOC > ____ are apparent; surrounded by epi/endo > bringing OPC/osteoblasts that start depositing bone and osteoclasts that eliminate cartilage

Answer 12

capillaries

Question 13

Endochondral Ossification: Key regulators of chondrocyte differentiation within the growth plate

1. Ihh: Secreted by ____ chondrocytes. Stimulates synthesis of ____. Regulates formation of ____.
2. PTHrP stimulates the proliferation of chondrocytes in the ____.
3. PTHrP inhibits the differentiation of ____ chondrocytes into ____ chondrocytes.
4. 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 ____)

Answer 13

proliferative zone
PTHrP
bone collar

reserve zone

proliferative zone
hypertrophic

type X collagen
VEGF

VIZ
length
cartilage

Question 14

Bone Growth: Bone Modeling

• ____: Alteration in the size and shape of bones during growth by the processes of bone formation and resorption:

1. Growth in width of the ____ long bone cylinder and expansion of the interior ____ cavity.
2. Shaping of the ends of the long bones to convert the broad ____ funnel into a narrow ____ cylinder.
3. 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.

Answer 14

modeling

diaphyseal
marrow
metaphyseal
diaphyseal
cranial vault

appositional
not possible

Question 15

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

Answer 15

periosteal
inside
haversian canals

Question 16

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.

Answer 16

second
growth hormone
anterior

estrogen
testosterone
intially
closure
faster
earlier
estrogen
longer
testosterone

fuse
21
18
oral contraceptives
premature

Question 17

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: ____.

Answer 17

throughout
3
25
4
bone remodeling unit (BRU)

Question 18

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?

Answer 18

osteoclast
cutting cone
osteoblast
closing cone
blood vessel
osteon

Question 19

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.

Answer 19

howship’s lacuna

progenitor

Question 20

Healing of Bone Fractures

1. Fracture hematoma: blood clot from broken blood vessels; swelling.

2. Soft callus formation: collagen and fibrocartilage is formed by ____ and infiltrated by capillaries at site of break; ____ differentiate into chondrocytes.
3. Callus ossification: soft callus replaced by hard woven bone callus in ~____ weeks; resembles the ____ process of ____ bone formation.
4. Remodeling: woven bone is replaced by compact bone in ~____ months; excess bone is removed by osteoclasts.

Answer 20

fibroblasts
periosteal

six
embryonic
endochondral

six

Question 21

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

Answer 21

synarthroses
fibrous
movement
amphiarthroses
cartilage
limited

diarthroses
synovial
free

vascularized

Question 22

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

Answer 22

condensation
differntiate
apoptosis
endochondral