European Journal of Orthodontics 1 (1979) 41-54

Published by Churchill Livingstone, London. European Orthodontic Society, 1979

Intrinsic regulation of the condylar

cartilage growth rate
Jeanne Stutzmann and Alexandre Petrovic
Laboratoire des Regulations de la croissance des Cartilages et des Os craniofaciaux, FRA 15
de I'lNSERM et Institut de Physiologie de la Faculte de M6decine, 4 Rue Kirschleger, 67085
Strasbourg Cedex, France.

Summary. The condylar cartilage was taken from intact 15-day-old male rats or from rats
with lateral pterygoid muscles resected 10 days previously. The condylar cartilage was put into
organ culture either whole or after partial or complete resection of the chondroblastic zone;
in addition the mitotic compartment of the condylar cartilage taken from intact rats was
associated in organ culture (a) with chondroblastic zones from condylar or angular cartilages
and from the spheno-occipital synchondrosis, (b) with some other tissues.

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According to the experimental findings, the not yet hypertrophied chondroblasts (i.e.
'functional chondroblasts') of a secondary cartilage send, permanently, a specific 'negative
feed-back signal' restraining the prechondroblast multiplication rate. One is dealing with an
intrinsic regulatory system. The acceleration of chondroblast maturation i.e. the diminution in
the number of the not yet hypertrophied chondroblasts, and the subsequent decrease of the
'prechondroblast multiplication restraining signal' represents an intermediary step for the
stimulating effect of mandibular postural hyperpropulsion, or of thyroxine on the condylar
cartilage growth rate.

Our previous experiments strongly suggest
that the growth rate of the condylar cartilage
is controlled, not only by general, regional
and local extrinsic factors (Charlier and
Petrovic, 1967; Charlier, Petrovic and Herr-
mann, 1968; Petrovic and Stutzmann, 1972;
Stutzmann and Petrovic, 1974; Petrovic,
Stutzmann and Oudet, 1975) but also by
intrinsic mechanisms governing the cell
multiplication rate (Stutzmann and Petrovic,
1975a; Stutzmann, 1976). Indeed, according
to our findings in organ culture, the presence
of chondroblasts, especially so-called 'func-
tional' chondroblasts, which synthesize carti-
laginous matrix but have not yet undergone
hypertrophy, has a restraining effect on the
multiplication of prechondroblasts. Such a
restraining effect is a cybernetic negative
This paper is supported by CRLINSERM no. 761354.
feed-back signal, being part of a regulatory
system (Stutzmann and Petrovic, 1975a).
Furthermore, the resection of the lateral
pterygoid muscle results, a few days after the
operation, in a significant decrease in the pre-
chondroblastic multiplication rate and then in
a reduction in thickness of both the mitotic
and the chondroblastic compartments of the
condylar cartilage (Charlier, Petrovic and
Herrmann, 1968; Petrovic and Stutzmann,
1972; Stutzmann and Petrovic, 1974). But
the basic finding is that chondroblastic
hypertrophy starts later and is less pro-
nounced than is usual. Thus we came to
investigate, in organ culture, the growth rate
of condylar cartilage taken from rats where
the lateral pterygoid muscle had been
resected 10 days previously.
The question arises: what could be the
nature of the 'negative feed-back signal ?' Is
42
it a chemical one, either specific, similar to
the 'chalones', or non specific originating in
the 'functional' chondroblasts or in the
cartilaginous matrix, or is it the manifes-
tation of cell density phenomena?
To collect more information on the
'negative feed-back' signal we carried out, in
organ culture, experiments on the association
between the mitotic compartment of the
condylar cartilage and various chondroblastic
zones (from condylar cartilage, angular
cartilage or spheno-occipital synchondrosis),
and between the mitotic compartment of the
condylar cartilage and some other tissues
(thyroid or tendon and muscle).
Material and methods
Our experiments were carried out on young
male rats of the Sprague-Dawley strain.
Condylar cartilage taken from rats with
lateral pterygoid muscle resected 10 days
previously and cultured as a whole or after
partial or complete resection of the
chondroblastic zone
The condylar cartilages were removed from
75 rats whose lateral pterygoid muscle had
been removed 10 days previously, and were
distributed in five experimental groups.
The animals of groups 1, 2, 3 and 4 were
sacrificed at the age of 15 days. The condylar
cartilages were removed and placed in organ
culture according to the technique of Petrovic
and Heusner (1961) and Heusner and Petrovic
(1964).
The experimental groups were consti-
tuted in the following way (Fig. 1): group 1:
complete condyles containing both carti-
laginous and bone tissue; group 2: condyles
where the endochondral bone zone was
resected; group 3: condyles where the distal
part of the chondroblastic zone was resected.
This distal part corresponds to the inferior
third of the condylar cartilage; and group 4:
condyles where the chondroblastic zone was
resected almost completely by removing two
thirds of the condylar cartilage.
After three days of organ culture, tritiated
CONDYLAR CARTILAGE GROWTH RATE
thymidine (2 uCi/ml, specific activity 25
Ci/mMole) was added to the culture medium
one hour before the end of the experiment.
The condylar explants were fixed, embedded,
cut serially in the sagittal direction and radio-
autographed according to the technique of
Kopriwa and Leblond (1962).
The animals of the fifth group were
sacrificed at the age of 18 days, at the
moment when the culture period was com-
pleted. One hour before sacrifice each
animal received an intraperitoneal injection
of 3 uCi of tritiated thymidine per gram of
body weight. The condylar cartilages were
removed and treated in the same way as the
condylar explants.
The condylar cartilage growth rate was
quantitatively evaluated by counting on every
tenth 5 \i section the total number of thymi-
dine-labelled cells in the mitotic compartment.
An equal number of histological sections was
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taken from each condyle. The results have
been statistically analysed and compared with
those obtained from condylar cartilages
taken from intact rats.
The labelled cell count, rather than a
labelling index, was chosen as a parameter of
the growth rate because the total number of
cells in the mitotic compartment of the
condylar cartilage varies; for instance, after
injections of STH or after mandibular postural
hyperpropulsion, the number of thymidine-
labelled cells in the mitotic compartment is
increased. Thus, the growth is related
directly and precisely to the total number of
dividing cells.
Mitotic compartment of the condylar
cartilage taken from intact rats and
associated in organ culture with various
chondroblastic zones or with other tissues
The different experimental designs are repre-
sented schematically in Fig. 2. Here also,
after three days of organ culture, tritiated
thymidine was added to the culture medium
one hour before the end of the experiment
and the growth rate was evaluated by
counting the total number of labelled cells in
the mitotic compartment.
 n
o
a
r
>

Condylar explants Condylar explants

taken from intact rats taken from rats with lateral pterygoid musdts rastctid 10 days prtviousti.
E

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fibrous capsule en
O
o
mitotic compartment
X
M SO

functional

proximal zone
chondroblists functional
of chondroblasts
CP

hu,pertrophic chondroblasK
distal zone

of chondroblasts hypertrophic
chondroblasts
CD chondroblasts

zone of endochondral
ossification
0

1 Tissue composition of the condylar explant on a 15-day-old rat.

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mitotic compartment mitotic compartment mitotic compartment
I. chondroblastic zone CP chondroblastic zone
chondroblastic zone
from another condylar cartilage from the angular cartilage
from the same condylar cartilage
(autoplastic association I
(homoplastic association)
HI 'TRC- CDII

mitotic compartment mitotic compartment mitotic compartment

distal part of the (upside down)
chondroblastic zone chondroblastic zone chondroblastic zone
(upside down)
(upside down)
from the same condylar cartilaqe
CP from the same condylar cartilage
from the same condylar cartilage
KM
8
mitotic compartment mitotic compartment mitotic compartment n
o
I . tendon
chondroblastic zone
from the spheno-occipitat synchondrosis thyroid
muscle JO
o
7>
CP : proximal p a r t : ' f u n c t i o n a r c h o n d r o b l a s t s ( F C ) CD : distal part : hypertrophic chondroblasts ( H O

O
m
Figure 2 Association between the mitotic compartment of the condylar cartilage and various chondroblastic zones or some other tissues. O

i
CONDYLAR CARTILAGE GROWTH RATE 45

Results culture is markedly decreased, whatever the

Condylar cartilage taken from rats with
lateral pterygoid muscle resected 10 days
previously and cultured as a whole, or with
partial or complete resection of the
chondroblastic zone
The statistical analysis of the results shows
that, compared with the condylar cartilage
in situ, the number of dividing cells in organ
experimental design (Table 1). Moreover, it
should be remembered that at the time the
in situ condylar cartilage is taken for organ
culture, its growth rate is already consider-
ably decreased due to the previous resection
of the lateral pterygoid muscle.
Regardless of the presence or the absence
of the lateral pterygoid muscle in donor rats,
the growth rate of the condylar cartilage will
vary, in organ culture, as a function of the

Table 1 Intrinsic regulation of the condylar cartilage growth rate

Number of dividing cells in the condylar cartilage. There were 15 observations for each group.

Experimental groups Mean Standard t-test

error

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Condyles taken from intact rats (m.pt.l.)
In situ 1512 31.09 M + CP + CD M + CP M
In organ culture
M + CP + CD + O 41 1.30 0.44 NS 6.27*** 13.54***
M + CP + CD 40 1.26 6.42*** 13.56***
M + CP 76 5.46 12.54***
M 576 39.53
Condyles taken from rats with lateral
pterygoid muscle resected 10 days previously (m.pt.l.o)
In situ 963 34.08 M+CP+CD M + CP M
In organ culture
M + CP + CD + O 20 1.45 0.87 NS 6.82*** 16.46***
M + CP + CD 22 0.76 6.72*** 16.43***
M + CP 81 8.79 13.93***
M 523 30.54

Comparison between 'growth rate of condylar cartilage taken from intact rats' and 'growth rate of condylar
cartilage taken from iats with lateral pterygoid muscle resected 10 days previously'
~~ m.pt.l.o
m.pt.l. ^~^~^^^ In situ In organ culture

M+CP+CD+O M+CP+CD M + C P M
In situ 11.89"*
In organ culture
M + CP + CD + O 11.69***
M + CP + CD 12.43***
M + CP 0.49 NS
M 1.06 NS

M = mitotic compartment: CP = proximal part of the chondroblastic zone: CD = distal part of the chondro-
blastic zone: O = zone of endochondral ossification: NS = difference not significant: *** = difference significant
at 0.001.
46
tissue composition of the explants. Indeed,
when the complete condyle explant is
cultured, the number of dividing cells, as
compared with the condylar cartilage in situ,
is markedly decreased: when only the bone
zone was resected, the number of dividing
cells remains markedly decreased: when the
distal part of the chondroblastic zone was
also resected (this part contains plain hyper-
trophic chondroblasts) the decrease in the
number of dividing cells was a little less
pronounced; when the chondroblastic zone
was resected almost entirely, the number of
dividing cells decreased still less. That is to
say, compared with that of the complete
condylar explant, the number of thymidine
labelled cells is greatly increased.
Analysis of the results of any organ
culture experimental design in which the
donor rats were intact compared with those
in which they had undergone resection of the
lateral pterygoid muscle, led to the conclusion
that there is a highly significant difference
between the two corresponding designs for
groups 1 and 2, i.e., the condylar cartilage
growth rate is lower when the donor rat has
undergone resection of the lateral pterygoid
muscle; and there is no significant difference
between the two corresponding designs for
groups 3 and 4.
In other words, whether the lateral
pterygoid muscle is present or is resected 10
days before the condylar cartilage is placed
into organ culture, the difference between the
two corresponding organ culture modalities
only appears when the distal third of the
condylar cartilage is present.
Mitotic compartment of the condylar
cartilage taken from intact rats and
associated in organ culture with various
chondroblastic zones or with some other
tissues
From the statistical analysis of the experi-
mental results (Fig. 3, Table 2) it can be
stated that the association of the cut-surface
side of the condylar cartilage mitotic compart-
ment with any tissue (chondroblastic zone of
CONDYLAR CARTILAGE GROWTH RATE
the condylar cartilage or of the angular
cartilage, spheno-occipital synchondrosis,
tendon and muscle or thyroid) brings about a
decrease in the number of dividing cells.
However, there are differences in the magnitude
of this decrease:
when the mitotic compartment is associated
with the chondroblastic zone taken from
the same condylar cartilage (Figs. 2.1 and
3.1) or from another condylar cartilage
(Figs. 2.2 and 3.2) the number of dividing
cells is very markedly decreased; but it
should be emphasized that this is not
significantly different from that observed
when the complete condylar cartilage is
cultured;
when the mitotic compartment is associated
with the chondroblastic zone of another
secondary cartilage (the angular cartilage,
Figs. 2.3 and 3.3), the number of dividing
cells is also decreased, but to a lesser
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extent;
when the mitotic compartment is associated
with the chondroblastic zone of a primary
cartilage, the spheno-occipital synchon-
drosis (Figs. 2.7 and 3.7) the decrease of the
growth rate is still smaller and it is not
significantly different from that observed
when the mitotic compartment is associated
with tendon and muscle (Figs. 2.8, 3.8)
or with thyroid (Figs. 2.9 and 3.9);
when the mitotic compartment is associated
with the chondroblastic zone of the condylar
cartilage in an inverted position (Figs. 2.4
and 3.4) - that is to say when the proximal
part of the chondroblastic zone is not in
immediate contact with the mitotic com-
partment - the decrease of the growth rate
is not so pronounced as when the mitotic
compartment is directly associated with the
proximal part of the chondroblastic zone
(Figs. 2.1, 2.2, 2.3, 3.1, 3.2 and 3.3). More-
over, no decrease at all in the number of
dividing cells is detected when the mitotic
compartment is associated in an inverted
position with the chondroblastic zone of
the condylar cartilage so that the cut-
surface side of the mitotic compartment
is not directly associated with the proximal
part of the chondroblastic zone.
CONDYLAR CARTILAGE GROWTH RATE 47

M M M
CP CP CP
CD CD CD

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condijlar cartilage as a whole or after partial or complete resection of the chondroblastic zone

association between the mitotic compartment of the condijlar cartilage and various
chondroblastic zones or some other tissues

Figure 3 Organ culture experiments.

Table 2 Organ culture experiments. Number of thymidine labelled cells in the mitotic compartment of the condylar cartilage
Treatment Number of Mean Standard t-test
observations error
M-(CP+CD) M-(CP+CD) M-(CD+CP) M-CD M-(CP+CD) M-S.O.S. M-T- M-Thy
cc ac ud ud Mus

Condylar cartilage as a whole or after partial or complete resection of the chondroblastic zone.
M 15 576 39.53 2.86" 0.39 NS 2.70* 2.29* 2.16*
M+CP 15 76 5.46
M+CP+
CD 15 40 1.26 3.63" 12.62*** 23.26*** 33.34*** 31.34*** 35.55***
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Association between the mitotic compartment of the condylar cartilage and various chondroblastic zones or some other tissues.
M-(CP+
CD)cc 15 48 1.88 11.96*** 22.84*** 32.50*** 30.61*** 34.69***
M-(CP+
CD) cc' 15 51 2.83 0.78 NS
M-(CP+
CD)ac 15 189 14.62 9.58*** 1.17 NS 10.19*** 13.86*** 14.22*** 14.39*** 15.46***
M-(CD +
CP) 15 213 13.64 13.25*** 13.52*** 13.70*** 14.81***
M-CD
upside
down 15 449 20.86 9.48*** 3.60** 0.64 NS 1.26 NS 1.56 NS
M upside 8
down- z
(CP+
CD) 15 559 22.28 3.68* 2.97** 2.82**
M-S.O.S. 15 465 12.68 0.85 NS 1.25 NS >g
M-Tendon- 9
Muscle 15 481 14.01 0.33 NS
M-Thyroid 15 487 12.51 r
M, mitotic compartment; CP, proximal part of the chondroblastic zone; CD distal part of the chondroblastic zone; cc, autoplastic association;
o
ra
cc', homoplastic association; ac, chondroblastic zone of the angular cartilage; S.O.S., chondroblastic zone of the spheno-occipital synchondrosis.
a

CONDYLAR CARTILAGE GROWTH RATE
Discussion
From these experiments it emerges that only
the 'functional'* not yet hypertrophied
chondroblasts of the condylar cartilage -
and, to some extent, of the angular cartilage -
have a strong restraining effect on the
chondroblastic multiplication rate. However,
to exert this effect the 'functional' chondro-
blasts have to be in direct contact with cells
of the mitotic compartment, without any
intermediate structure such as the articular
zone. Without doubt such an effect is related
to a negative feed-back signal of a regulatory
system. The best way to account for the
restraining effect on the prechondroblastic
multiplication rate is to postulate the
existence of a 'signal' of a chemical nature
originating in the proximal part of the
chondroblastic zone of the secondary cartilage.
At present, we have no idea of the nature
and the origin of the negative feed-back
signal: it could be a specific substance like a
'chalone' (Bullough, 1962) or a non-specific
substance having its provenance either in the
'functional' chondroblasts or in the carti-
laginous matrix.
The next problem was to explain the
slight decrease in the number of dividing cells
observed when the mitotic compartment of
the condylar cartilage is associated with any
tissue different from secondary cartilage
chondroblasts. In the light of general cell
physiology, the phenomenon should be
connected with cell density but it could be
associated with a membrane-to-membrane
contact phenomenon like the 'contact inhibi-
tion' (Abercrombie and Heaysman, 1954). In
addition, there might be feed-back signal of a
chemical nature. Do the associated tissues
prevent the release into the culture medium
of the substance produced by the small
portion of the proximal part of the chondro-
blastic layer located along the cells of the
mitotic compartment? (This is conceivable
because it is practically impossible to remove
* Histologically, the synthesis of the specific carti-
laginous matrix is mainly observed in the proximal
part of the chondroblastic zone. For this reason, we
call the involved cells 'functional' chondroblasts.
49
the chondroblastic zone completely when
preparing the mitotic compartment for
cultivation.) Whatever the answer to these
questions, we detected the existence of an
intrinsic regulatory mechanism controlling
the growth rate of the condylar cartilage. The
cell density as such cannot account for all the
findings reported above. It is highly probable
that the 'negative feedback signal' is of a
chemical nature.
When the complete condylar cartilage
was placed into the organ culture (with or
without endochondral bone), the prechondro-
blastic growth rate was lower in the explants
originating from rats whose lateral pterygoid
muscle had previously been resected. Such a
difference is not detectable when the condylar
explant contains the mitotic compartment
alone or is connected to the proximal part of
the chondroblastic zone.
How are the experimental findings to be
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interpreted ?
The in vivo results in Table 1, confirm
our previous finding (Petrovic and Stutzmann,
1972; Stutzmann and Petrovic, 1974) that the
resection of the lateral pterygoid muscle
brings about a very important slowing down
in the condylar cartilage growth rate.* In
addition, after resection of this muscle, the
stem-cells we call skeletoblast cells do not
continue to differentiate into prechondro-
blasts (Stutzmann and Petrovic, 1975b). Our
previous investigations have shown that the
number of cell divisions a prechondroblast
can undergo before becoming a 'functional'
chondroblast is limited. In other words, in
the weeks following the muscle resection, the
stock of pre-existing prechondroblasts will be
* The influence on condylar growth exerted by the
lateral pterygoid muscle implies transmission of
information either of a biomechanical nature, such
as tension, or of a chemical or even electrical nature
(Charlier, Petrovic and Herrman, 1968; Petrovic
and Stutzmann, 1972). The intensity of the condylar
response should reflect the intensity of the stimulus
(Petrovic, Stutzmann and Oudet, 1975). The menisco-
temporal elastic ligament with its condylar branch
appears to be one of the main actuators in its
control action over the condylar cartilage growth
rate, i.e., in maintaining fine occlusal adjustment
(Petrovic and Stutzmann, 1977).
50 CONDYLAR CARTILAGE GROWTH RATE

progressively exhausted (Petrovic and Stutz- We suggest that a consequential - but

mann, 1972; Stutzmann and Petrovic, 1974;
Stutzmann, 1976). Thus, the cessation of the
differentiation of the 'skeletoblasts' into pre-
chondroblasts, can account for the decrease
in the number of prechondroblasts available
for cell division.
The resection of the lateral pterygoid
muscle also results in a slowing down of the
chondroblastic maturation rate and hyper-
trophic intensity. This means that chondro-
blastic hypertrophy starts later and is less
pronounced than is usual. Consequently,
even a portion of the distal part of the chon-
droblastic zone will contribute to the 'negative
feedback signal', restraining the prechondro-
blastic multiplication rate. It is easy to under-
stand that, in organ culture, only in the
presence of the distal part of the chondro-
blastic zone is the 'negative feedback signal'
actually greater when the condylar explant
certainly not the only - effect of the lateral
pterygoid muscle activity consists of stimu-
lating the chondroblastic maturation and
hypertrophy rate. Thus, it is partly by
reducing the 'negative feedback signal' that
this muscle will stimulate the prechondro-
blastic multiplication rate. This hypothesis is
partly supported by our resection experiments
of the menisco-temporal ligament with its con-
dylar branch (Petrovic and Stutzmann, 1977).
The concept of an intrinsic regulation of
the condylar cartilage growth rate is not only
a biological curiosity. It offers an interpre-
tation model of experimental data of interest
in orthodontics and medicine.
The first example concerns the effects of
the mandibular postural hyperpropulsor, an
appliance able to stimulate the condylar
cartilage growth rate (Charlier, Petrovic and
Herrman, 1968; Charlier, Petrovic and

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is taken from rats where the lateral pterygoid
muscle has been resected than from intact rats.
One could object that after resection of
the lateral pterygoid muscle the condylar
cartilage size becomes smaller but that the
'feedback' signal' should also be decreased
and the prechondroblast growth rate should
be increased. However, it should be remem-
bered that the number of prechondroblasts
able to divide is progressively decreasing
because skeletoblasts cease to differentiate
into prechondroblasts.
Herrmann-Stutzmann 1969; Petrovic, 1974).
The total number of cells increases simul-
taneously in the mitotic compartment and the
chondroblastic zone, but the most interesting
fact is that the chondroblast hypertrophy
starts earlier than usual (Fig. 4.3); this
means that the part corresponding to func-
tional chondroblasts, i.e., the part producing
the 'negative feedback signal', is decreased.
Thus, according to our concept of an intrinsic
regulation of the prechondroblastic multi-
plication, the increased growth rate in the

Figure 4 Intrinsic regulation of the condylar cartilage growth rate variations of the chondroblastic hypertrophy rate
and subsequent variations of the 'prechondroblastic multiplication restraining signal' (the feedback signal).
1. Controls. Negative feedback signal of usual intensity; usual condylar cartilage growth rate.
2. Thyroxine low doses (2 to 3 week experiments). Chondroblastic hypertrophy, i.e. maturation rates, accelerated; con-
sequent decrease in the number of 'functional'chondroblasts. Negative feedback signal decreased. Increase in the condylar
cartilage growth rate.
3. Postural hyperpropulsor (2 to 4 week experiments). Chondroblastic hypertrophy starts earlier; consequent decrease
in the number of 'functional' chondroblasts. Negative feedback signal decreased. Increase in the condylar cartilage growth
rate.
4. Unilateral increase in the occlusal vertical dimension (a cast gold overlay cemented on the maxillary molar group).
Opposite side: no change in the chondroblastic maturation and hypertrophy rates. Negative feedback signal of usual
intensity. Usual condylar cartilage growth rate. Same side: chondroblastic hypertrophy starts earlier; consequent
decrease in the number of 'functional' chondroblasts. Negative feedback signal decreased. Increase in the condylar
cartilage growth rate.
CONDYLAR CARTILAGE GROWTH RATE 51

1. Controls 2.Thyroxine (low doses 1

( 3 weeks)

dividinq
cells

functional

chondroblasts

hupertrophic I

chondroblasts

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feed - back signal feed-back signal

of usual intensity decreased

3. Postural hyperpropulsor 4. Unilateral increase in the occlusal vertical dimension

(2 to U weeks) oleft side oa cast-gold overlay cemented
on the maxillary right molar group

dividing
cells

functional \ (V5 _ ^ .
chondroblastsj

hypertrophic

chondroblasts

feed-back signal feed-back signal feed-back signal

decreased of usual intensity decreased

52
condylar cartilage could be due, pro parte, to
the decrease in the magnitude of the 'feed-
back signal'.
According to our recent investigations
(Petrovic and Stutzmann, 1977; Petrovic,
1977), the earlier commencement ofchondro-
blast hypertrophy as produced in the young
rat by the mandibular postural hyperpro-
pulsor seems to result from the increased
postural activity of the lateral pterygoid
muscle and from the simultaneously increased
iterative activity of the menisco-temporal
fraenum and of the menisco-condylar liga-
ment with its condylar branch.
Unilateral increase in the occlusal vertical
dimension which can be effected by cementing
a cast gold overlay on the maxillary molar
group in rats produces, on the homolateral
condylar cartilage, effects very similar to
those obtained with the postural hyper-
propulsor (Schlienger, 1978). It should also
be stated that no change in the hypertrophy
rate could be observed in the condylar
cartilage located on the opposite side; and its
growth rate was not significantly modified.
The second example concerns the effects
of low doses of thyroxine. It is generally
STH-- SOMATOMEDIN
HITOTIC COMPARTMENT :
(1) Increase in the
skeletoblasts and prechondroblasts
multiplication rate
(2) Acceleration of the differentiation of
skeletoblasts into prechondroblasts
(3) Stimulation of the cartilage matrix synthesis
Figure 5 Main site of action.
CONDYLAR CARTILAGE GROWTH RATE
accepted that thyroxine does not stimulate the
cell division rate in primary cartilages but
only the chondroblastic maturation rate. Our
histological investigations have shown that
thyroxine also stimulates the maturation rate
of the chondroblasts in the condylar cartilage
with the result that the chondroblastic zone
becomes much narrower. But what is peculiar
in the condylar cartilage is that, when given
in low doses, thyroxine also stimulates the cell
division rate (Stutzmann, Petrovic and Oudet,
1975; Stutzmann, 1976). The concept of an
intrinsic regulation of the condylar cartilage
growth rate can explain this peculiarity of the
thyroxine action: the acceleration of the
chondroblastic maturation rate results in a
decrease in the number of functional chon-
droblasts. Thus, the magnitude of the 'negative
feedback signal' will be decreased and, con-
sequently, the prechondroblastic multiplica-
tion will be less restrained and the number of
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dividing prechondroblasts will be increased.
One last observation should be reported:
without the acceleration of the maturation
rate, we have never observed an increased
growth rate with orthopaedic or orthodontic
appliances, or with thyroxine. On the other
ORTHOPEDIC AND ORTHODONTIC APPLIANCES,
THYROXINE
CHONDROBLASTIC ZONE :
Acceleration of
hypertrophy and maturation rate
Decrease in the feed-back signal
Increase in
prechondroblasts multiplication rate
CONDYLAR CARTILAGE GROWTH RATE
hand, the earlier commencement of chondro-
blastic hypertrophy did not occur when the
growth hormone was injected. Indeed, as
represented in Fig. 5, the primary site of
action of the STH-somatomedin complex
appears to be the mitotic compartment itself.
This hormone complex stimulates the multi-
plication of skeletoblasts and prechondro-
blasts and favours the differentiation of
skeletoblasts into prechondroblasts. Con-
sequently, the number of 'functional' and
hypertrophic chondroblasts also increases.
In this way it becomes easy to understand
the positive multiplicative interaction between
STH-somatomedin and the mandibular pos-
tural hyperpropulsor (Petrovic, Stutzmann
and Oudet, 1975): the number of prechondro-
blasts available to undergo increased cell
division is greater than normal.
Conclusions
The experimental results reported above
strongly suggest the existence of an intrinsic
regulatory mechanism of the condylar carti-
lage growth rate. The quantitative analysis
demonstrates, beyond any doubt, that the cell
density, as such, cannot account completely
for our findings and that there must be a
'negative feedback signal' originating from
the proximal part of the chondroblastic
zone and exerting a restraining effect on the
prechondroblastic multiplication rate.
The concept of an intrinsic regulation of
the condylar cartilage growth rate can help
to explain the effects of some orthopaedic
or orthodontic appliances as well as of a
hormone (thyroxine).
The earlier commencement of chondro-
blastic hypertrophy and the subsequent
decrease in the prechondroblast restraining
signal appear to be important intermediary
steps in the growth stimulating effect of the
mandibular postural hyperpropulsor. The
acceleration of the chondroblastic maturation
rate is, in a similar way, an intermediary
step for the growth rate stimulating effect of
thyroxine.
53
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