ORIGINAL ARTICLE

Gingival response to orthodontic force

Meir Redlich, DMD, MSc,a Shmuel Shoshan, PhD,b and Aaron Palmon, DMD, PhDc
Jerusalem, Israel

Orthodontic tooth movement is brought about by prolonged application of force on the attachment
apparatus. This results in cellular and extracellular changes within the periodontium. As shown in numerous
studies, tooth movement is achieved after the remodeling of alveolar bone and the response of the
periodontal ligament to the mechanical force. Although gingival changes have also been found to be an
important factor in the overall response, the effect of orthodontic tooth movement on the gingiva has been
investigated to a lesser extent. Unlike bone and periodontal ligament, which regain their original structure
after removal of force, the gingival tissue does not regain its pretreatment structure, a fact on which a
hypothesis has been made that tooth relapse after removal of retention may be associated with changes in
the gingiva. The present review summarizes available data on the effect of orthodontic force on collagen,
elastin, and collagenase in the gingiva and its relevance to understanding the mechanism of tooth relapse.
(Am J Orthod Dentofacial Orthop 1999;116:152-8)

T he gingiva is composed of epithelium and
underlying connective tissue that is attached to the
external part of the alveolar bone and the supracrestal
region of the tooth.
Collagen fibers are the main structural component
in the extracellular matrix (ECM) of the gingiva. They
account for about 60% of total tissue protein.1 Healthy
gingiva contains interstitial collagen type-I (90%), col-
lagen type-III (8%) and collagen types IV, V, VI, and
VIII (2%).2-5 Ultrastructural analysis reveals two pat-
terns of gingival collagen arrangement2: (1) large thick,
mostly parallel collagen-type-I fibers interconnected by
thin fibrils6 (Fig 1). This arrangement of the collagen
fibers confers strength and rigidity to this tissue, which
sustains heavy masticatory forces; and (2) short and
thin fibers in a fine reticular network located mainly
under the epithelial basement membrane and around
blood vessels.
The collagen fibers in the gingiva are grouped
according to their origin and insertion. The most impor-
tant distinct groups are the dentogingival fibers and the
transseptal fibers. The latter bridge the shortest distance
between the supraalveolar cementum of adjacent teeth,
In partial fulfillment of the degree of PhD for Dr Redlich.
From the Hebrew University-Hadassah Faculty of Dental Medicine, founded by
the Alpha Omega Fraternity, Jerusalem, Israel.
aDepartment of Orthodontics and Connective Tissue Research Laboratory,
Department of Oral Biology.
bConnective Tissue Research Laboratory, Department of Oral Biology.
cDepartment of Oral Biology.
Reprint requests to: Dr Meir Redlich, Department of Orthodontics, Hebrew
University-Hadassah, Faculty of Dental Medicine, PO Box 12277, Jerusalem
91220, Israel
Copyright © 1999 by the American Association of Orthodontists.
0889-5406/99/$8.00 + 0 8/1/95060
152
irrespective of tooth anatomy and alveolar bone mor-
phology.7,8
Gingival collagen has a high turnover rate. In the
rat, collagen has a half life of about 10 days.9 A partic-
ularly high turnover rate is that of the transseptal fibers,
which is at least as high as that of collagen in the peri-
odontal ligament.10 Furthermore, both collagens type I
and type III are metabolized at a similar rate indicating
a common metabolic control mechanism of these col-
lagens.11 The high rate of gingival collagen metabo-
lism is a physiologically intrinsic characteristic associ-
ated with the functional burden of the tissue, enabling
it to maintain its integrity by an equilibrium between
collagen synthesis and degradation.
Apart from the collagen network, the gingiva also
contains a network of elastic fibers, comprising 6% of the
total human gingival protein. This network is composed
of three different types of fibers, namely elastic, elaunin,
and oxytalan fibers, which provide the gingiva with the
elastic properties needed to oppose pressure.12 The three
types of fibers differ in their state of maturation after
biosynthesis and are distinguished by morphologic, tinc-
torial, and mechanical differences, as follows:
1. The elastic fiber, the most important component
in the elastic system, is composed of two mor-
phologic ultrastructurally distinct components:
(a) the protein elastin that is a highly insoluble
morphologically amorphous component, and the
only component in the system that endows elas-
tic property to the tissue13; (b) a microfibrillar
component consisting of fibrils 10 to 12 nm in
diameter.13 This is a glycoprotein located pri-
marily at the periphery of the amorphous elastin
protein.
American Journal of Orthodontics and Dentofacial Orthopedics
Volume 116, Number 2
Fig 1. Scanning electron photomicrograph of transseptal region of intact gingiva in dog to show lon-
gitudinally sectioned large collagen fiber bundles (CF) interconnected with thinner fibers (arrow
heads). (Bar = 0.1 mm.)
2. The elaunin fiber is made of less mature elastin
protein in which the microfibrils are still within
the amorphous component.14
3. The oxytalan fiber is a collection of microfibrils
lacking any elastic properties and, therefore, does
not contribute to the elastic properties of the tis-
sue.14,15 Interestingly, immunoassays have failed
to show elastic fibers in the human periodontal lig-
ament that contain oxytalan fibers only.16 Recent-
ly, it has been demonstrated that either oxytalan
fibers or the microfibrillar components of the elas-
tic fiber are associated with type VI collagen.5
The ECM of the gingiva also contains proteogly-
cans, such as chondroitinsulfate, dermatansulfate, and
heparansulfate.17,18 The proteoglycans represent a fam-
ily of macromolecules consisting of a central core pro-
tein, to which polysaccharide chains called gly-
cosaminoglycan (GAG) are covalently attached.19 Pro-
teoglycans are important organizers of the ECM and
their major role is to maintain the structural integrity of
the connective tissue.20
The currently identified glycoproteins of the gingi-
va are fibronectin, laminin, and SPARC (secreted pro-
tein, acidic and rich in cysteine), also known as
osteonectin.21,22
Fibronectin and laminin, are extracellular multiadhe-
sive proteins. Fibronectin binds to collagens, proteogly-
cans, and to cells via specific cell surface receptors
known as integrins.23 Fibronectin is important for cell
migration and cell differentiation and plays an important
role during wound healing by attracting macrophages and
other immune cells to the injured area.24,25
Redlich, Shoshan, and Palmon 153
Laminin is present in all basal laminae including
gingival basement membrane. It has binding sites with
high affinity to the other components of the basal lam-
ina thus providing stability to this structure.26
The calcium binding glycoprotein SPARC is an
extra cellular protein that disrupts cell-ECM interac-
tion.27 In vivo, it is found at sites of cell proliferation,
migration, and morphogenesis.28 SPARC has been
described in both periodontal ligament and gingiva,
which are dynamic tissues,29 and at the periphery of a
healing wound (Shoshan, 1994, unpublished). It is
assumed that SPARC protein is associated with the
high turnover rate of collagen within these tissues.29
The most abundant cells in the gingiva are fibro-
blasts. Their volume comprises 5.6% of the total gin-
gival volume.30 Other cells residing in the gingiva are
macrophages, lymphocytes, mast cells, endothelial
cells, and nerves.
The function of fibroblasts and other cells are inti-
mately associated with the ECM, which provides the
proper microenvironment for the cellular activity.31
This effect of the ECM is mediated by specific cell
receptors via the cell cytoskeletal network to the cell
nuclei.31 The functional integrity of gingival tissue is
obviously maintained by the cell-ECM interactions.
THE EFFECT OF FORCE ON THE GINGIVA
Clinical Observations
Gross gingival changes are observed after closure
of an extraction site or rotation movement or excessive
labial tooth movement.
Adjacent to an extraction site, the teeth are approx-
154 Redlich, Shoshan, and Palmon
imated, resulting in an accumulation of gingival tissue
and enlargement of the interdental papilla.32 The tissue
accumulation is the result of both retraction and com-
pression. The gingiva retracts together with the tooth
movement, although at a lesser distance.32 At the
mesial surface of the orthodontically retracted tooth, a
triangular patch of red tissue appears.33 This red patch
is considered to be the reduced enamel epithelium that
has been peeled off the tooth surface.33 Adjacent to the
accumulated gingival tissue, vertical invaginations or
clefts of both the epithelium and the connective tissue
are formed on the buccal and lingual aspects. Many of
these deformities persist for years after treatment.34,35
During orthodontic rotation movement, unlike dur-
ing the closure of extraction site, the gingiva rotates
both to the same degree and in the same direction as the
tooth.36 Extensive rotational movement causes the
rotated gingiva to be compressed in the interdental area
at the direction of rotation.
Clinically, both the approximated and rotated teeth
are prone to relapse toward the pretreatment positions
after removal of force (retention), thus indicating their
instability. Completion of orthodontic treatment after
extraction brings about reopening of the extraction site
and is a typical pattern of tooth relapse. It is assumed
that the compressed transseptal fibers in the hyperplas-
tic gingiva have become folded between the teeth, and
this is the main cause for the reopening relapse.37
Indeed, surgical removal of the excess gingiva prevents
tooth relapse.35
These patterns of gingival response to tooth move-
ment show wide variations in their clinical appear-
ances. However, the variations are modifications of the
same pattern of gingival response, rather than any basi-
cally different responses.33
From the clinical point of view special attention should
be drawn to the possible consequences of excessive labial
tooth movement, especially that of incisors, which may
bring about an irreversible gingival recession.38
Histologic Findings
The assumption that the observed tooth relapse is
associated with clinical changes in the gingiva led to
histologic studies being carried out in order to investi-
gate the microstructural nature of these changes. Histo-
logically, discontinuation of the transseptal fibers is
seen after a tooth has been extracted. During healing of
the extraction site, newly formed collagen fibers bring
about a reestablishment of continuity of the transseptal
fibers thus creating a fibrous bridge connecting the sep-
arated teeth.39
The orthodontic approximation of the teeth at the
extraction site is accompanied by papillary epithelial
American Journal of Orthodontics and Dentofacial Orthopedics
August 1999
hyperplasia.40 The newly formed transseptal collagen
fibers are coiled and compressed.8 and have a “football
shaped” appearance.37 According to another study,
however, the new transseptal fibers have a normal mor-
phologic appearance after closure of the extraction
site.35 In addition, loss of collagen fibers is reported in
the hyperplastic gingiva after closure of the extraction
site.40,41 In the transseptal region, distant to the alveo-
lar crest, a significant increase in oxytalan fibers35 as
well as increased levels of GAG have been described.41
The latter are also implicated in elevating the elastic
properties of the gingival tissue at the extraction site.41
In orthodontic rotational movement, an increase in
oxytalan fibers and reorientation (“stretching”) of the
gingival collagen fibers has been reported.36,42 The
clinical instability of the rotated tooth, which almost
always relapses, has been attributed to the stretched
collagen fibers. According to this assumption, the
stretched fibers that originate from the gingiva and are
inserted into the cementum, pull the tooth back toward
its pretreatment position. To relieve the rotated tooth
from forces exerted by the assumed stretched fibers
and to ensure its stability after release of retention, a
procedure of gingival circumferential fiberotomy has
been introduced.43 The surgical procedure prevents the
rotational relapse and has no adverse effect on peri-
odontal health.44
The effect of orthodontic force on the synthesis rate
of gingival fibroblasts has been studied histochemical-
ly with tritiated proline.45 The incorporation of H3 pro-
line in the gingiva has been measured after an ortho-
dontic enlargement of the interdental space of maxil-
lary incisors in rats. It has been reported that proline
uptake of the newly formed collagen increased signifi-
cantly in both the lamina propria and transseptal region
thus suggesting that orthodontic force stimulates colla-
gen production in the gingiva.
Ultrastructural Analysis
The effect of orthodontic tooth movement on both
collagen and elastin in the gingiva has been investigat-
ed also by ultrastructural analysis.
The ultrastructure of interdental gingivae of human
premolars has been analyzed by transmission electron
microscopy (TEM) after application of force on these
teeth.46 The results show that the diameter of collagen
fibers significantly increased in both pressure and ten-
sion aspects when compared to untreated controls. In
some areas within the compressed papilla, degraded
collagen fibers have been observed. They have been
longitudinally split and without the typical banding
pattern. On the pressure aspect of the gingiva, a slight
increase in the number and size of elastic fibers has
American Journal of Orthodontics and Dentofacial Orthopedics Redlich, Shoshan, and Palmon 155
Volume 116, Number 2

Fig 2. Detection of collagen type I (col I) and collagenase (coll-ase) transcription in gingival fibro-
blasts before and after induction of mechanical force. PCR analysis was carried out using oligonu-
cleotides primers specific to collagen type I and collagenase. C, before induction of force; E, after
force. The PCR products were separated on ethidium bromide-stained agarose gel and pho-
tographed under ultraviolet illumination. Actin mRNA was also assessed as an internal control. On
the right-hand side, densitometric analysis of the PCR products. (M. Redlich et al. Arch Oral Biol,
1998;43:313-6, with permission).

also been seen. On the tension aspect, however, as well
as in the untreated controls, only a few elastic fibers
have been observed.
A similar gingival response to orthodontic force has
also been found during rotation movement in the dog.6
There too the collagen fibers appear torn, disorganized,
and laterally spaced in some areas, whereas in other
areas the diameter of the collagen fibrils has been sig-
nificantly increased. In addition, an increased number
of elastic fibers has been seen in proximity to the torn
collagen fibers.
Molecular Analysis
The effect of mechanical force on gene transcrip-
tion of collagen type I and tissue collagenase (MMP1-
matrix metalloproteinase 1) has been studied on gingi-
val fibroblasts in vitro using the reverse-transcriptase
polymerase chain reaction (RT-PCR).47 Canine gingi-
val fibroblasts have been grown in culture, and a pres-
sure analogous to orthodontically induced force has
been elicited on the cultured cells by gravitational force
during centrifugation. The speed/duration conditions of
the centrifuge after which 90% of the cells remained
vital were chosen for the experiments. Such conditions
were 1000 RPM and 90 minutes. Increasing the cen-
trifuge speed to 1500 RPM or doubling it to 2000 RPM
caused 30% and 50% cell death, respectively. Speed of
1000 RPM and duration of 120 or 150 minutes caused
20% and 30% cell death, respectively. The force exert-
ed on the cells after centrifugation of 1000 RPM dur-
ing 90 minutes is equivalent to force of 0.167 kg/1g of
cell mass (according to F = [V2:R] × M, where F =
force, V = speed, R = radius of the rotor, M = mass).
This force magnitude is within the range of common
orthodontic forces.48 Under these conditions, the tran-
scription level of collagen type I has been significantly
increased whereas that of tissue collagenase has been
significantly decreased (Fig 2).
These changes after pressure on gingival fibroblasts
indicate a disturbed equilibrium between collagen syn-
thesis and degradation required to maintain adequate
tissue stability at the pretranslational level (Fig 3).
Changes in the Phenotype of Gingival Fibroblasts
and Tooth Relapse
Unlike bone and PDL, the gingival tissue is not
resorbed after orthodontic treatment, but it is com-
pressed and consequently retracts. The fact that
orthodontic force does not bring about gingival
resorption prevents the formation of periodontal
pockets and subsequent detachment of the tooth from
the gingiva.
156 Redlich, Shoshan, and Palmon American Journal of Orthodontics and Dentofacial Orthopedics
August 1999

Fig 3. Schematic presentation of the effect of force on up-down regulation of collagen type I (col I)
and collagenase (MMP1) in cultured gingival fibroblasts. A, Collagen synthesis and degradation in
equilibrium under normal conditions (col I↔MMP1). B, Collagen type I is pretranslationally up-regu-
lated and collagenase is down-regulated after application of force on cultured fibroblasts.

Tooth relapse after removal of retention indicates an
undesirable force being exerted on the tooth. It is
assumed that this force is generated within the attach-
ment apparatus affected by the orthodontic forces.49
This relapse, after closure of an extraction site or rota-
tion movement requires clinical solutions in order to
overcome the instability of the orthodontically treated
teeth. The fact that surgical procedures, such as gin-
givectomy or fiberotomy do overcome the instability of
the treated teeth means that the force causing relapse is
“stored” within the gingival tissue.
The clinically observed gingival changes after tooth
movement are accompanied by a significant increase in
the relative amount of both interstitial collagen and
elastin.
As for the clinically manifested relapse of teeth
after rotation movement, an ultrastructural study
showed that it cannot be attributed to “stretched” colla-
American Journal of Orthodontics and Dentofacial Orthopedics
Volume 116, Number 2
gen fibers.6 It was also found6 that unlike in normal
gingiva, a significantly increased amount of elastic
fibers is present in the compressed gingiva after rota-
tion. The newly formed elastic fibers that are part of the
ECM and that are not connected to the tooth, increase
the elasticity of the gingiva. An explanation for the
mechanism of relapse has been proposed, namely the
compressed gingiva that rotates with the tooth during
the rotation movement and in which an increased
amount of elastic fibers is formed exerts pressure on
the tooth leading to relapse after the release of reten-
tion. Indeed, the surgical procedure of fiberotomy dis-
connects the compressed gingiva from the tooth thus
preventing tooth relapse. The compressed gingiva
resembles compressed rubber, which after the release
of compression returns to its original dimensions.
The effect of the orthodontic force on gingiva after
closure of an extraction site is similar to that after rota-
tion. The relapse, which is in this case manifested by
reopening of an extraction site is also most likely due
to increased elasticity of the compressed gingiva
brought about by biosynthesis of both new elastic
fibers46 and GAG.41 In that case, surgical procedures
on the gingiva prevent the relapse similarly to that of
fiberotomy after rotation. It is assumed that in both
types of relapse the gingiva undergoes an elastic defor-
mation capable of affecting the stability of the adjacent
teeth.
An increased biosynthesis of both collagen and
elastin after pressure has been observed also in other
tissues.50-52 In specimens taken from human abdominal
striae alba from multiparous and obese women, the
number of elastic fibers as well as the diameter of col-
lagen fibers, mostly made of collagen type I, have been
increased relative to that in normal skin.50 It has been
suggested that this change in the phenotype of the
fibroblasts has evolved as a functional demand due to
abnormal pressure acting on the skin.50 A similar effect
of mechanical stress on increased collagen and elastin
biosynthesis is observed also in the media of arter-
ies.51,52 Chronically elevated arterial blood pressure,
reflecting transient mechanical force, brings about an
increase in both elastin and collagen deposition.
The molecular analysis of the effect of force on gin-
gival fibroblasts demonstrates that mechanical force
causes an increase in the expression of collagen type I
gene, and a decrease in that of the collagenase gene.47
Similarly, it has also been reported that tension modu-
lates the phenotype of human dermal fibroblasts, and
that the steady-state mRNAs levels of procollagen
alpha 1(I), and procollagen alpha 2(I) and elastin are
significantly higher, whereas that of collagenase is
decreased in fibroblasts cultured under tension.53
Redlich, Shoshan, and Palmon 157
The presently reviewed data indicate the impor-
tance of understanding the mechanisms of tooth
relapse after the different orthodontic procedures in
order to further improve the clinical outcome of such
interventions. Thus, the changes in collagen and elastin
in the gingiva after orthodontic force are of important
clinical relevance. The question whether the metabo-
lism of gingival collagen is renormalized after the
removal of force has yet to be answered, as well as
another unsolved question of the long-term metabolism
of the newly synthethized elastic fibers. Under normal
conditions, the elastic fibers hardly degrade,54 which
means that the observed increased elastica in the gingi-
va after orthodontic treatment is there to stay for a long
time.
The fact that proper elastic fibers are not noticed in
the PDL poses the question whether orthodontic force
will affect the ECM also of that dental structure.
CONCLUSIONS
One should consider the fact that two disparate
processes occur in the gingiva after the transduction of
the orthodontic force. First, there is an injury of the
connective tissue manifested by torn and ripped colla-
gen fibers. Second, the genes of both collagen and
elastin are activated whereas that of tissue collagenase
is inhibited, thus, affecting the ECM of the gingiva.
Therefore, the relapse is probably associated with
increase in elasticity of the gingiva that is being retract-
ed and compressed in direction of the tooth movement.
In order to better understand the relapse and per-
haps to prevent it by nonsurgical procedures, one
should investigate the extra and intracellular pathways
of cell-ECM interactions through which the orthodon-
tic force affects the gingiva.
We acknowledge the valuable comments offered by
Prof Adrian Becker (Department of Orthodontics) in
preparing this manuscript.
REFERENCES
1. Page RC. Macromolecular interactions in the connective tissue of the periodontium.
In: Slavkin H, Bavetta L, editors. Developmental aspects of oral biology. New York:
Academic Press; 1972. p. 291-308.
2. Chavrier C, Couble ML, Magloirre H, Grimaud JA. Connective tissue organization of
healthy human gingiva. Ultrastructural localization of collagen types I-III-IV. J Peri-
odont Res 1984;19:221-9.
3. Romanos G, Schroter-Kermani C, Hinz N, Bernimoulin JP. Immunohistochemical
distribution of the collagen types IV,V,VI and glycoprotein laminin in the healthy rat,
Marmoset (Callithrix jacchus) and human gingivae. Matrix 1991;11:125-32.
4. Salonen J, Oda D, Funk S, Sage EH. Synthesis of type VIII collagen by epithelial cells
of human gingiva. J Periodont Res 1991;26:355-60.
5. Everts V, Niehof A, Beertsen W. Type VI collagen is associated with microfibrils and
oxytalan fibers in the extracellular matrix of periodontium, mesenterium and perios-
teum. J Periodont Res 1998;33:118-25.
6. Redlich M, Rahamim E, Gaft A, Shoshan S. The response of supra-alveolar gingival
collagen to orthodontic rotation movement in dogs. Am J Orthod Dentofacial Orthop
1996;110:247-55.
7. Kusters ST, Kuijpers-Jagtman AM, Maltha JC. An experimental study in dogs of
158 Redlich, Shoshan, and Palmon
transseptal fiber arrangement between teeth which have emerged in rotated or non-
rotated positions. J Dent Res 1991;70:192-7.
8. Erikson BE, Kaplan H, Aisenberg MS. Orthodontics and transeptal fibers: a histolog-
ical interpretation of repair phenomena following the extraction of first premolars with
retraction of the anterior segment. Am J Orthod Oral Surg 1945;31:1-20.
9. Sodek J, Ferrier JM. Collagen remodeling in rat periodontal tissues: compensation for pre-
cursor reutilization confirms rapid turnover of collagen. Collagen Rel Res 1988;1:11-21.
10. Deporter DA, Svoboda ELA, Howley TP, Shiga A. A quantitative comparison of col-
lagen phagocytosis in periodontal ligament and transseptal ligament of the rat peri-
odontium. Am J Orthod 1984;85;519-22.
11. Sodek J, Limeback HF. Comparison of the rates of synthesis, conversion and matura-
tion of type I and type III collagens in rat periodontal tissues. J Biol Chem
1979;254:10496-502.
12. Chavrier C, Hartmann DJ, Couble ML, Herbage D. Distribution and organization of
the elastic system fibers in healthy human gingiva: ultrastructural and immunohisto-
chemical study. Histochemistry 1988;89:47-52.
13. Rosenbloom J, Abrams WR, Mecham R. Extracellular matrix 4: the elastic fiber.
FASEB J 1993;7:1208-18.
14. Cleary EG, Gibson MA. Elastic tissue, elastin and elastin associated microfibrils. In:
Comper WD, ed. Extracellular matrix, Vol 2. Amsterdam: Harwood Academic Press;
1996. p. 95-140.
15. Fullmer HM, Lillie RD. The oxytalan fiber: a previously undescribed connective tis-
sue fiber. J Histochem Cytochem 1958;6:425-30.
16. Johnson RB, Pylypas SP. A re-evaluation of the distribution of the elastic meshwork
within the periodontal ligament of the mouse. J Periodont Res 1992;27:239-49.
17. Bartold PM, Wiebkin OW, Thonard JC. Proteoglycans of human gingival epithelium
and connective tissue. Biochem J 1983;211:119-27.
18. Purvis JA, Embery G, Oliver WM. Molecular size distribution of proteoglycans in
human inflamed gingival tissue. Arch Oral Biol 1984;29:513-9.
19. Dorfman A. Proteoglycans biosynthesis. In: Hay ED, ed. Cell biology of extracellular
matrix. New York: Plenum Press; 1981. p. 115-38.
20. Ruoslathi E. Structure and biology of proteoglycans. Ann Rev Cell Biol 1988;4:
229-55.
21. Termine JD, Kleinman HK, Whitson SW, Conn KM, McGarvey ML, Martin GR.
Osteonectin, a bone specific protein linking mineral to collagen. Cell 1981;26:99-105.
22. Dziadek M, Paulsson M, Aumailly M, Timpl R. Purification and tissue distribution of
a small protein (BM-40) extract from basement membrane tumor. Eur J Biochem
1986;161:455-64.
23. Hynes RO. Integrins: versatility, modulation, and signal in cell adhesion. Cell
1992;69:11-25.
24. Stenman S, Vaheri A. Distribution of major connective tissue protein, fibronectin, in
normal human tissue. J Exp Med 1978;147:1054-64.
25. Hynes RO. Fibronectins. New York: Springer-Verlag; 1990.
26. Timpl R. Structure and biological activity of basement membrane proteins. Eur J
Biochem 1989;180:487-502.
27. Lane TF, Iruela-Arispe ML, Johnson RS, Sage EH. SPARC is a source of copper bind-
ing peptides that stimulates angiogenesis. J Cell Biol 1994;125:929-43.
28. Sage EH, Decker J, Funk SE, Chow M. SPARC: a Ca 2+binding extracellular matrix
associated with endothelial cell injury and proliferation. J Mol Cell Cardiol
1989;21(S):13-222.
29. Salonen J, Domenicucci C, Goldberg HA, Sodek J. Immunohistochemical localization
of SPARC (osteonectin) and denatured collagen and their relationship to remodeling
in rat dental tissues. Arch Oral Biol 1990;35:337-46.
30. Schroeder HE, Munzel-Pedrazzoli S, Page RC. Correlated morphometric and bio-
chemical analysis of early chronic gingivitis in man. Arch Oral Biol 1973;18:899-923.
31. Boudreau N, Bissel MJ. Regulation of gene expression by extracellular matrix. In:
American Journal of Orthodontics and Dentofacial Orthopedics
August 1999
Comper WD, editor. Extracellular matrix, Vol 2. Amsterdam: Harwood Academic
Press; 1996. p. 246-61.
32. McCollum AGH, Preston CB. Maxillary canine retraction, periodontal surgery, and
relapse. Am J Orthod 1980;78:610-22.
33. Atherton JD. The gingival response to orthodontic tooth movement. Am J Orthod
1970;58:179-86.
34. Rivera AL, Tulloch JFC, Gingival invagination in extraction sites of orthodontic
patients: their incidence, effects on periodontal health, and orthodontic treatment. Am
J Orthod 1983;83:468-76.
35. Edwards JG. The prevention of relapse in extraction cases. Am J Orthod 1971;60:
128-41.
36. Edwards JG. A study of the periodontium during orthodontic rotation of teeth. Am J
Orthod 1968;54:441-61.
37. Parker GR. Transseptal fibers and relapse following bodily retraction of teeth: a his-
tologic study. Am J Orthod 1972;61:331-44.
38. Steiner GG, Pearson JK, Ainamo J. Changes of the marginal periodontium as a result
of labial tooth movement in monkeys. J Periodontol 1981;52:314-20.
39. Chase SW, Revesz J. Reestablishment of transseptal fibers following extraction. J
Dent Res 1944;23:333-6.
40. Kurol J, Ronnerman A, Heyden G. Long-term gingival conditions after orthodontic
closure of extraction sites: histological and histochemical studies. Eur J Orthod
1982;4:87-92.
41. Ronnerman A, Thilander B, Heyden G. Gingival tissue reactions to orthodontic closure
of extraction sites: histologic and histochemical studies. Am J Orthod 1980;77:620-5.
42. Boese LR. Increased stability of orthodontically rotated teeth following gingivectomy
in Macaca nemestrina. Am J Orthod 1969;56:273-90.
43. Edwards JG. A surgical procedure to eliminate rotational relapse. Am J Orthod
1970;57:35-46.
44. Rinaldi SA. Changes in free gingival level and sulcus of human periodontium follow-
ing circumferential supracrestal fibertomy. Am J Orthod 1979;75:46-53.
45. Boisson M, Gianelly AA. Collagen synthesis in rat gingiva during tooth movement.
Am J Orthod 1981;80:289-99.
46. Franchi M, Daloya U, De Pasquale V, Caldini E, Graziani E, Borea G, Ruggeri A.
Ultrastructural changes of collagen and elastin in human gingiva during orthodontic
tooth movement. Bull Group Int Rech Sci Stomatol et Odontol 1989;32:139-43.
47. Redlich M, Palmon A , Zaks B, Edel J, Rayzman S, Shoshan S. The effect of mechan-
ical force on the transcription levels of collagen type I and collagenase in cultured
canine gingival fibroblasts. Arch Oral Biol 1998;43:313-6.
48. Reitan K, Rygh P. Biomechanical principles and reactins. In: Graber TM, Vanarsdall RL,
eds. Orthodontics: current principles and techniques. St. Louis: Mosby; 1994. p. 96-192.
49. Reitan K. Tissue rearrangement during retention of orthodontically rotated teeth.
Angle Orthod 1959;29:105-13.
50. De Pasquale V, Franchi M, Govoni P, Guizzardi S, Raspanti M, Poppi V, Ruggeri A.
Striae Albae: a morphological study on the human skin. Bas Appl Histochem
1987;31:475-86.
51. Sudhir K, Wilson E, Chatterjee K, Ives HE. Mechanical strain and collagen potentiate
mitogenic activity of angiotensin II in rat vascular smooth muscle cells. J Clin Inevst
1993;92;3003-7.
52. Keeley FW, Alatawi A, Cho A. The effect of wall stress on the production and accu-
mulation of vascular elastin. In: Tamburro AM, Davidson JM, editors. Elastin: chem-
ical and biological aspects. Galatina Congedo Editore: 1990. p. 339-56.
53. Lambert CA, Soudant EP, Nusgens BV, Lapiere CM. Pretranslational regulation of
extracellular matrix macromolecules and collagenase expression in fibroblasts by
mechanical force. Labor Inves 1992;66:444-51.
54. Powell JT. Dilatation through loss of elastin. In: The cause and management of
aneurysms. Greenhalgh RM, Marrick JA, editors. London: Saunders; 1990.