10. Cartilage and Bone Growth Flashcards
what is ENDOCHONDRAL OSSIFICATION
when BONE REPLACES existing CARTILAGE
what is INTRAMEMBRANOUS OSSIFICATION
when BONE develops directly from MESENCHYME or FIBROUS CONNECTIVE TISSUE
(skull, clavicle)
HYALINE CARTILAGE has 2 MAIN ROLES in BONE (2 forms):
- GROWTH PLATE CARTILAGE
- ARTICULAR CARTILAGE
is GROWTH PLATE CARTILAGE stable or transient
TRANSIENT
- destined to be REPLACED BY BONE
is ARTICULAR CARTILAGE stable or transient
STABLE
6 STEPS of FORMATION of ARTICULATION (joint)
- MESENCHYMAL CELLS CONDENSE
- Joint Site Determination
- INTERZONE is formed : where mesenchymal cells GATHER
- mesenchymal cells then DIFFERENTIATE into CHONDROCYTES
- INTERZONE is formed : where mesenchymal cells GATHER
- Chondrocytes secrete CYTOKINE GDF5 which INDUCES CAVITATION (formation of an EMPTY SPACE within a solid object)
- Morphogenesis (shaping)
- JOINT FORMATION
may become SYNOVIAL JOINT eg knee joint
which CYTOKINE INDUCES CAVITATION during formation of ARTICULATION
GDF5
GDF5 expressing cells (joint progenitors) undergo different SIGNALLING PATHWAYS to form different parts.
what signalling will form SYNOVIAL LINING & LIGAMENTS:
- ANTI-CHONDROGENIC SIGNALLING
- Wnt signalling (some)
form SYNOVIAL LINING & LIGAMENTS
GDF5 expressing cells (joint progenitors) undergo different SIGNALLING PATHWAYS to form different parts.
what signalling will form ARTICULAR CARTILAGE at the END of bone
- ANTI-CHONDROGENIC SIGNALLING
- NOTCH signalling (some)
form ARTICULAR CARTILAGE
GDF5 expressing cells (joint progenitors) undergo different SIGNALLING PATHWAYS to form different parts.
what signalling will form GROWTH PLATE cartilage
GDF under the regulation of SOXs
CHONDROGENIC
GDF5 expressing cells (joint progenitors) undergo different SIGNALLING PATHWAYS to form different parts.
cells that undergo ANTI-CHONDROGENIC signalling can take two pathways.
some take…to form…
some take… to form…
either
- WNT SIGNALLING to form SYNOIVAL LINING & LIGAMENTS
or
- NOTCH SIGNALLING to form ARTICULAR CARTILAGE
GDF5 expressing cells (joint progenitors) undergo different SIGNALLING PATHWAYS to form different parts.
is CHONDROGENIC pathway to form GROWTH PLATE, what Transcription Factor is requires
SOXs
steps of ENDOCHONDRAL OSSIFICATION
- MESENCHYMAL CELLS CONDENSE
- DIFFERENTIATE into CHONDROCYTES
- some chondrocytes DIFFERENTIATE into HYPERTROPHIC CHONDROCYTES
- PERICHONDRIAL CELLS DIFFERENTIATE into OSTEOBLASTS, forming BONE COLLAR.
HYPERTROPHIC CHONDROCYTES undergo APOPTOSIS and BLOOD VESSEL COMES IN (vascular invasion) - OSTEOBLASTS and BLOOD SUPPY allow primary bone formation - PRIMARY SPONGIOSA FORMED
- chondrocytes continue to PROLIFERATE, lengthening the bone
- (postpartum) SECONDARY OSSIFICATION CENTRE
forms through INVASION of BLOOD SUPPLY (vascular invasion) into head of bone
in the growth plate PROLIFERATING CHONDROCYTES form…
COLUMNS
COLUMN FORMATION of CHONDROCYTES in the GROWTH PLATE is driven by which CHEMOKINE
and how
IHH - INDIAN HEDGEHOG
- stimulates column formation through ACTIVATION of PARATHYROID HORMONE RELATED PROTEIN
when CHONDROCYTES become HYPERTROPHIC CHONDROCYTES they change MATRIX formation and SWITCH from COLLAGEN TYPE II to …
COLLAGEN TYPE 10 (X)
What happens after HYPERTROPHIC CHONDORCYTES under APOPTOSIS
OSTEOBLASTS COME IN and form PRIMARY SPONGIOSA
What are SECRETED in HYPERTROPHIC CHONDROCYTES
and what do they do
METALLOPROTEASES
- REMODEL CARTILAGE so bone can INVADE
what happens to the GROWTH PLATE in ADULT BONE
ENDS / CLOSES
(bone formation there instead)
BONE GROWTH occurs through the..
GROWTH PLATE CARTILAGE
4 STAGES of CHONDROCYTES
- PROLIFERATING chondrocyte
- PREHYPERTROPHIC chondrocyte
- HYPERTROPHIC chondrocyte
- TERMINAL chondrocyte
(apoptose)
CHONDROCYTES and their different stages are REGUALTED by..
TRANSCRIPTION FACTORS
(SOX9
Pthrp -> IHH
SOX5/6
RUNX2/3
MEF2C/D
Wnt/Beta-Catenin)
name of one of the TRANSCRIPTION FACTORs that REGULATE a PROLIFERATING CHONDROCYTE
SOX9
also SOX5/6
and chemokine IHH
for PREHYPERTROPHIC and HYPERTROPHIC CHONDROCYTES which TRANSCRIPTION FACTOR is SWITCHED ON
RUNX2/3
(REPLACES SOXs - switched off)
what is DIFFERENT about INTRAMEMBRANOUS OSSIFICATION as opposed to Endochondral
MESENCHYMAL CELLS condense and become OSTEOBLASTS
- WITHOUT CHONDROCYTE FORMATION
NO CARTILAGE INTERMEDIARY
TRANSCRIPTION FACTORS used in INTRAMEMBRANOUS OSSIFICATION
no SOXs
skeletogenic cell -> immature osteoblast
RUNXS
OSX
(IHH)
immature osteoblast -> mature osteoblast
ATF4
INTRAMEMBRANOUS OSSIFICATION is dependent on..
MESENCHYMAL CONDENSATION
IHH increases the length of proliferative columns by:
directly..
indirectly..
Directly acting at the top of these columns present in the growth
plate
Indirectly through the actions of PTHrP (parathyroid hormone related protein)
which HORMONES are IMPORTANT in BONE GROWTH
- CORRECT LEVELS of these hormones are important
GROWTH HORMONE,
GLUCOCORTICOIDS eg cortisol,
THYROID HORMONE,
SEX HORMONES
why is PARATHYROID HORMONE important in BONE GROWTH
CALCIUM-REGULATING
MAINTAINS the levels of CALCIUM (INCREASES)
- STIMULATES both RESORPTION and FORMATION of BONES
why is CALCITRIOL an important hormone in BONE GROWTH
DERIVED FROM VITAMIN D (activated by PTH)
STIMULATES INTESTINES to ABSORB CALCIUM
- INCREASES CALCIUM
why are SEX HORMONES important in BONE GROWTH
STRENGTH
LOW ESTROGEN/TESTOSTERONE leads to WEAKER BONES
why is ARTICULAR CARTILAGE IMPORTANT
SPREAD the LOAD
& REDUCE FRICTION
friction free movement
why is LOAD important
MAINTAINS (ARTICULAR) CARTILAGE
long periods of time without load (eg in bed) can cause degradation of articular cartilage
BONE and CARTILAGE are designed to … and … MECHANICAL LOADING
RESIST mechanical loading
& ADAPT TO mechanical loading
CARTILAGE GROWS by 2 means:
- INTERSTITIAL
- APPOSITIONAL
what is INTERSTITIAL GROWTH
GROWTH FROM WITHIN
- In EPIPHYSEAL GROWTH PLATE
chondrocytes divide, cartilage enlarges
what is APOSITIONAL GROWTH
NEW LAYERS of CARTILAGE being ADDED to the surface
- via PERICHONDRIUM
- BONE INCREASES SIZE
which type of CARTILAGE GROWTH occurs in the EPIPHYSEAL GROWTH PLATE
INTERSTITIAL
BONE can only INCREASE IN SIZE by which type of growth
APPOSITION
bone does NOT increase in size by interstitial growth
why do we need CHONDROCYTES in ENDOCHONDRAL OSSIFICATION
OSTEOBLASTIC APPOSITION is NOT SUFFICIENT to SUSTAIN RAPID LONGITUDINAL GROWTH
the Capacity for LONGITUDINAL GROWTH is MAINTAINED by the PERSISTENCE of..
EPIPHYSEAL GROWTH CARTILAGES
CARTILAGE undergoes…
(which growth)
INTERSTITIAL GROWTH and is REPLACED BONE
CHILDHOOD and ADOLESCENCE BONES are SCULPTED by a process called..
MODELLING
which allows for the formation of new bone at one site and the removal of old bone from another site within the SAME bone
what happens to HYPERTROPHIC CHONDROCYTES in ENDOCHONDRAL OSSIFICATION
DIE (APOPTOSIS) in the calcified matrix surrounding them
