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 179

Human Palatal and Tuberosity Mucosa

as Donor Sites for Ridge Augmentation

Claudia Dellavia, DDS, PhD1 Root coverage and soft tissue aug-
Giano Ricci, DDS2 mentation procedures are based
Letizia Pettinari, PhD3 on bilaminar techniques using a
Cristina Allievi, DDS, PhD4 pedicle flap to cover a subepithe-
Fabio Grizzi, PhD5 lial connective tissue autograft,1–4
Nicoletta Gagliano, PhD6 thus providing an additional blood
supply compared with free gin-
Since different clinical outcomes of periodontal bilaminar surgeries using the
palate or the maxillary tuberosity as connective tissue (CT) donor sites have gival grafts and resulting in more
been observed, tissues grafted with CT from the palate or the tuberosity 1 predictable functional and esthetic
year after surgical procedures for ridge augmentation were compared with outcomes.1,2,5 The graft thickness is
nongrafted tissues by using morphologic and molecular methods. Collagen an important factor for obtaining
content and matrix metalloproteinases 1 and 2 expression were similar in optimal esthetics: a 1.5- to 2-mm
tissues and cultured fibroblasts from the palate and tuberosity, although with
thickness is needed to maintain
interindividual differences. In contrast, differences in collagen cross-linking
and maturation in the tuberosity fibroblasts were observed, suggesting a vascularization, promote wound
possible role in determining hyperplastic responses in some patients. (Int J healing, and provide long-term
Periodontics Restorative Dent 2014;34:179–186. doi: 10.11607/prd.1929) graft stability.1,6,7 The main donor
site is the connective tissue (CT)
obtained from the palatal area be-
tween the first premolar and the
first molar, but its removal is tech-
1Adjunct Professor, Department of Biomedical, Surgical and Dental Sciences,
Università degli Studi di Milano, Milan, Italy. nique sensitive, unpleasant for pa-
2Private Practice, Florence, Italy. tients, and sometimes limited in
3Postdoctoral Student, Department of Biomedical Sciences for Health, Faculty of
size.8 The maxillary tuberosity can
Medicine and Surgery, Università degli Studi di Milano, Milano, Italy.
4Postdoctoral Student, Department of Biomedical, Surgical and Dental Sciences,
be used as an alternative,5,6,8 al-
Faculty of Medicine and Surgery, Università degli Studi di Milano, Milano, Italy. lowing surgeons to collect thicker
5Biologist, Laboratories of Quantitative Medicine, IRCCS Istituto Clinico Humanitas,
grafts and, in concomitance with
Rozzano, Milan, Italy. other oral interventions, reduce
6Associate Professor, Department of Biomedical Sciences for Health,

Università degli Studi di Milano, Milan, Italy.

patient discomfort from a sec-
ond surgery.5,8,9 Differences were
Correspondence to: Dr Claudia Dellavia, Department of Biomedical, Surgical and found in the clinical outcomes of
Dental Sciences, Università degli Studi di Milano, Via Mangiagalli 31, 20133 Milan, Italy;
localized alveolar ridge augmen-
fax: +390250315387; email: claudia.dellavia@unimi.it.
tation with soft tissue harvested
©2014 by Quintessence Publishing Co Inc. from either the palate or tuberosity

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180
approximately 1 year after sur-
gery.10 The gingival tissues grafted
with palatal mucosa showed a sig-
nificant initial shrinkage or contrac-
tion but remained stable over time
with a good esthetic result. In con-
trast, the gingival tissues grafted
with tuberosity CT were dimension-
ally stable in the first few months,
then progressively tended to a hy-
perplastic reaction and assumed
a not esthetically pleasing white
tissue patch appearance.8,10 Since
the mechanism responsible for a
different maturation of the grafted
tissue using the two donor sites is
still unclear, this study aimed to (1)
compare the palatal and the max-
illary tuberosity mucosa in healthy
subjects, with particular attention
to collagen content and turnover-
related pathways; and (2) analyze
the morphology of sites augment-
ed with subepithelial CT grafted
from either the palate or tuber-
osity, along with the ability to re-
model extracellular matrix (ECM) in
cultured fibroblasts obtained from
the same grafted tissues to under-
stand the mechanisms responsible
for different clinical outcomes.
Method and materials
Experimental model
Fourteen healthy women aged 49
to 68 years with a Class I defect who
underwent surgical procedures for
ridge augmentation were divided
in two groups: group A received
a graft from the palatal mucosa
taken from the palate between the
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second and first premolar where the
thickness of the mucosa is greater
(palatal donor site: n = 7; mean
age: 58.6 ± 6.1 years) and group B
received a graft from the maxil-
lary tuberosity (tuberosity donor
site: n = 7; mean age: 59.7 ± 8.3
years). All subjects were free from
periodontal disease and did not
use hormonal contraceptives or
hormonal replacement medica-
tions. All patients signed a consent
form to participate in the experi-
ment. The study was conducted in
accordance with the ethical princi-
ples of the World Medical Associa-
tion Declaration of Helsinki and the
local ethics committee.
Surgical technique
For ridge augmentation, the epi-
thelium and the adipose tissue
were removed with a no. 15 blade
from a 3.5-mm-thick graft, a split-
thickness flap was raised on the
buccal aspect of the surgical area
without the use of vertical inci-
sions, and the CT graft was kept
in position with a combination of
vertical and horizontal mattress
and single 5-0 vycril sutures. One
year after surgery, an epithelium-
CT biopsy specimen of all grafted
sites was obtained for histologic
and molecular analyses, as were bi-
opsy specimens from healthy pala-
tal mucosa and maxillary tuberosity
from nongrafted oral sites for com-
parisons. A clinical measurement
of the grafted site was carried out
presurgery, after 1 month, after 1
year (concomitantly with plastic
surgery), and 9 months after the
plastic surgery by insertion of a
periodontal probe at a 90-degree
angle in the tissue using a calibrat-
ed surgical stent retained by the
adjacent teeth with a fixed refer-
ence point.
Histochemistry and image
analysis
Tissue fragments were fixed in 4%
phosphate-buffered formalin and
routinely processed for paraffin
embedding. Sections were stained
with hematoxylin-eosin to evaluate
the tissue morphology and with
Sirius red to specifically stain colla-
gen and to calculate the area frac-
tion index (AA%).
Cell cultures
Gingival fibroblasts were obtained
from hard palate and tuberos-
ity biopsy specimens and from the
grafted tissue, as previously de-
scribed.11
Real-time RT-PCR
Total RNA was isolated by Tri-
Reagent. mRNA levels of collagen
type I and type III (COL-I, COL-III),
long lysyl hydroxylase 2 (LH2b),
and matrix metalloproteinase 1
and 2 (MMP-1, MMP-2) were as-
sessed. GAPDH was used as a
housekeeping gene, and gene ex-
pression levels were normalized on
its expression.
 181

a b c

Fig 1 Microphotographs showing palatal (a, c, e) and tuber maxillae (b, d, f) mucosa. (a
and b) Hematoxylin-eosin staining; original magnification ×10. (c and d) Sirius red staining;
original magnification ×10. (e and f) Polarized light; original magnification ×10.

d e f

Slot blot Statistical analysis Results

COL-I, COL-III, and MMP-1 protein
levels secreted by palate and tu-
berosity fibroblasts were assessed
by slot blot.12
SDS-zymography
Concentrated culture media were
analyzed by SDS-zymography, as
previously described.12
For morphologic (AA%) and mo-
lecular data, descriptive statistics
(mean and SD) were computed for
the CT from the palatal mucosa,
the tuberosity, and the grafted mu-
cosa for groups A and B. Compari-
sons between the two nongrafted
sites were performed by Wilcoxon
signed-rank test for paired samples
and between grafted tissues from
different donor sites by Wilcoxon
sum-rank test for unpaired sam-
ples. A level of significance of 5%
(P ≤ .05) was used.
Nongrafted palatal and
maxillary tuberosity mucosa
Morphologic analysis
All specimens from the nongrafted
palatal and maxillary tuberosity mu-
cosa showed a healthy structure,
without any inflammation or acan-
thosis, and normal epithelial crests
(Figs 1a and 1b). The CT in the pala-
tal lamina propria was loose and
highly vascularized (Fig 1c), but in
the tuberosity was more dense and
poorly vascularized (Fig 1d). In both

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182

COL-I mRNA COL-III mRNA

Normalized fold expression

Normalized fold expression

10 20

8 16

6 12

4 8

2 4

0 0
Palate Tuberosity Palate Tuberosity

COL-I protein levels COL-III protein levels

250,000 80,000

Densitometric units
Densitometric units

200,000
60,000
150,000
40,000
100,000

50,000 20,000

0 0
Palate Tuberosity Palate Tuberosity

LH2b mRNA LH2b/COL-I mRNA

Normalized fold expression

4.0 1,200
LH2b/COL-I mRNA %

1,000
3.0
800
2.0 600
400
1.0
200
0 0
Palate Tuberosity Palate Tuberosity

Fig 2 COL-I and COL-III mRNA and protein levels, LH2b gene expression, and the LH2b/COL-I mRNA ratio in palate and tuberos-
ity human fibroblasts. Immunoreactive bands revealed by the Amplified Opti-4CN substrate were scanned densitometrically. Data were
obtained from confluent human gingival fibroblasts used between the fourth and fifth passage and cultured in duplicate for 72 hours for
molecular evaluations. Changes in mRNA were normalized on GAPDH gene expression. Values are means ± SDs for duplicate samples.

sites, collagen fiber bundles ran in
all directions, as confirmed by anal-
ysis from a polarized microscope
(Figs 1e and 1f). Image analysis of
Sirius red-stained sections revealed
that collagen content (AA%) was
similar in the CT of the tuberosity
(80.91% ± 8.77%) compared with
the palate (75.57% ± 7.68%).
Molecular analysis
COL-I and COL-III gene expression
tended to decrease in the tuberosi-
ty compared with palate fibroblasts
(P < .05 and P > .05, respectively)

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 183

MMP-1 mRNA MMP-2 mRNA

Normalized fold expression

Normalized fold expression

4 10

8
3
6
2
4
1
2

0 0
Palate Tuberosity Palate Tuberosity

MMP-1 protein levels MMP-2 activity

300,000
600,000

Densitometric units
250,000
Densitometric units

500,000
200,000
400,000
150,000
300,000
100,000
200,000
100,000 50,000

0 0
Palate Tuberosity Palate Tuberosity

Fig 3 MMP-1 and MMP-2 gene expression, MMP-1 protein levels, and MMP-2 activity in cultured palate and tuberosity human fibroblasts
and in their cell culture supernatants. MMP-1 protein levels secreted by palate and tuberosity fibroblasts were assessed by slot blot using
a monoclonal antibody to MMP-1. Immunoreactive bands revealed by the Amplified Opti-4CN substrate were scanned densitometrically.
Changes in mRNA were normalized on GAPDH gene expression. Values are means ± SDs for duplicate samples.

(Fig 2). COL-I and COL-III protein
levels were similar in fibroblast su-
pernatants (Fig 2), although they
increased, respectively, in 57%
and 66% of tuberosity fibroblast
supernatants. The overall LH2b
mRNA levels tended to increase in
the tuberosity fibroblasts and were
upregulated in 54% of samples
(Fig 2), although with a wide in-
terindividual variation. The over-
all LH2b/COL-I mRNA ratio in the
tuberosity fibroblasts resulted in
four-fold increased (Fig 2), and
was increased in 69% of tuberos-
ity compared to palate fibroblasts.
MMP-1 and MMP-2 mRNA levels
tended to decrease in tuberos-
ity compared to palate fibroblasts
(P > .05) (Fig 3). MMP-1 protein lev-
els decreased in 50% of tuberosity
fibroblast supernatants, compared
with palate fibroblasts, but the
mean levels were similar in both
palate and tuberosity fibroblast
supernatants (Fig 3), possibly due
to interindividual variations. A simi-
lar pattern was observed for the
mean MMP-2 activity analyzed by
SDS-zymography (Fig 3).
Grafted tissue
Clinical outcomes
All cases were treated in the maxil-
la: 65% in the anterior region, 25%
in the premolar area, and 10% in
the molar area. At surgery all de-
fects were completely filled, and a
primary intention healing occurred.
After 1 year, the sites grafted with
CT from the palate did not show
any hyperplastic reaction and
some displayed a reduction in vol-
ume (Fig 4a). In contrast, the sites
grafted with CT from the maxillary

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184

a b

LH2b mRNA LH2b/COL-I mRNA

1.5
Normalized fold expression

Normalized fold expression

150

1.0 100

0.5 50

0 0
Normal Hyperplastic Normal Hyperplastic
response response
c d
Fig 4 Postsurgical outcomes in patients receiving a graft from (a) the palatal or (b) the tuberosity mucosa. A morphology consistent with a
hyperplastic response is evident in group B. LH2b gene expression (c) and the LH2b/COL-I mRNA ratio (d) in fibroblasts obtained from graft-
ed tissue with good esthetic results or after hyperplastic reaction. LH2b/COL-I mRNA ratio is expressed as a percentage compared to palate
fibroblasts (100%). Changes in mRNA levels were normalized on GAPDH gene expression. Values are means ± SDs for duplicate samples.

Table 1 Thickness of the oral mucosa (mean ± SD)

After 9 mo after
Presurgery 1-mo postsurgery 1-y postsurgery plastic surgery plastic surgery
Graft donor site (mm) (mm) (mm) (mm) (mm)
Palate (group A) 2.0 ± 0.2 5.5 ± 0.3 4.9 ± 0.6 4.7 ± 0.4 4.7 ± 0.3
Tuberosity (group B) 2.1 ± 0.2 5.8 ± 0.2 6.8 ± 1.1 5.6 ± 0.8 6.4 ± 1.0

tuberosity had a dimensional sta- Morphologic analysis Molecular analysis

bility, with some showing a tenden- Morphologic analysis of post-
cy to a more evident hyperplastic surgical grafted specimens from
response (Fig 4b), and underwent groups A and B revealed a nor-
plastic surgery. Nine months later, mal tissue architecture with only
these sites exhibited a tendency to slight differences in collagen con-
rebound, recapturing 70% of the tent within the connective com-
tissue volume eliminated by plastic partment. In group A (palate), the
surgery (Table 1). mean AA% was 53.78% ± 6.10%,
while in group B (tuberosity), it was
60.72% ± 9.30% (P > .05).
LH2b gene expression was simi-
lar in fibroblasts from groups A
and B (Fig 4c). In contrast, the
LH2b/COL-I mRNA showed a four-
fold increase in fibroblasts from the
tuberosity (group B) characterized
by a hyperplastic and not estheti-
cally pleasing outcome (Fig 4d).

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Discussion
The structure of the palatal and tu-
berosity mucosa and of the fibro-
blast phenotype from these two
donor sites was analyzed. Although
data are available on the macro-
scopic and microscopic features of
the palatal soft tissue,6,7,10,13–16 only
a few studies analyzed the histolo-
gy and the expression of genes and
proteins involved in collagen turn-
over of the tuberosity mucosa.8,9
Light microscopy analysis re-
vealed that the CT of the tuberosi-
ty was denser and less vascularized
than the palatal lamina propria, as
already reported by Studer et al9
and Arcidiacono and Ricci.10 A high
collagen content was observed
in both the palate and tuberos-
ity without significant differences
between sites, possibly due to
interindividual differences, al-
though limited published data are
available for comparison.11,17–20
Posttranslational hydroxylation
of collagen by lysyl hydroxylase
(LH) is a key mechanism influenc-
ing collagen maturation, extracel-
lular matrix stability, and, therefore,
collagen content. LH2b gene ex-
pression was investigated since
this is the major form expressed
in all tissues and is generally over-
expressed in fibrotic processes,
being responsible for the overhy-
droxylation of the COL telopep-
tides, forming COL pyridinoline
cross-links and thus contributing
to unwanted COL accumulation.
The LH2b/COL-I mRNA ratio indi-
cates the gene expression of LH2b
relative to COL-I and therefore the
susceptibility of collagen to un-
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dergo hydroxylation.21,22 The pres-
ent data on LH2b mRNA levels and
the LH2b/COL-I mRNA ratio sug-
gest that, in tuberosity, COL could
be susceptible to cross-linking at
a higher extent and therefore less
susceptible to degradation by
MMPs, possibly leading to its ex-
cessive accumulation.23 Interstitial
collagenase or MMP-1 cleaves the
native triple helical region of in-
terstitial COL, allowing its further
digestion by less specific protein-
ases such as MMP-2.24,25 No sig-
nificant differences in MMP-1 and
MMP-2 mRNA and the protein lev-
els in tuberosity and palate fibro-
blasts were observed, but MMP-1
activity downregulation in half of
tuberosity cell culture supernatants
suggests that reduced intersti-
tial collagen degradation and the
concomitant tendency to a higher
LH2b/COL-I mRNA ratio could rep-
resent a relevant mechanism likely
responsible for collagen accumu-
lation in the tuberosity connective
compartment.
To better understand the
mechanisms leading to hyperplas-
tic response after grafting, the
tissue structure and LH2b gene
expression in fibroblasts obtained
from grafted tissues were analyzed
with different clinical outcomes.
Sirius red-stained collagen was
similar in grafts from palatal and
tuberosity mucosa, but a tenden-
cy was observed for greater LH2b
mRNA levels and LH2b/COL-I
mRNA ratio in grafted tissues char-
acterized by a non-esthetically
pleasing outcome, suggesting that
possible differences in collagen
maturation could act as the major
185
determinants in the hyperplastic
response after grafting with the
tuberosity mucosa. Interestingly,
in one sample in group B showing
an evident hyperplastic response,
a high LH2b/COL-I mRNA value
was observed in the postgrafted as
well as in the nongrafted maxillary
tuberosity mucosa. Future studies
on a larger number of subjects are
needed to confirm this observa-
tion, since it could be relevant for
understanding if the grafting using
the tuberosity could predispose
patients to a hyperplastic response.
The observed differences in gene
expression between palatal and
tuberosity mucosa fibroblasts were
not statistically significant possibly
due to the interindividual variabil-
ity, according to the previously de-
scribed heterogeneity of gingival
fibroblast subpopulations. Hetero­
geneous responses to various
stimuli were observed in gingival
fibroblasts in relation to collagen
turnover and to the responsiveness
to drugs, suggesting the existence
of different gingival fibroblast phe-
notypes and leading to the cell
subpopulation theory.26,27
Conclusion
Considered as a whole, these pre-
liminary data could provide the
basis for future studies aimed at
investigating the role of structural
and molecular differences between
the palatal and tuberosity CT when
used as donor sites in bilaminar
periodontal procedures. From a
clinical point of view, when choos-
ing a CT graft from the tuberosity,
Volume 34, Number 2, 2014
186
it is advisable to thin it down to a
thickness of 3 mm, even if the de-
fect to be treated is 5 mm deep, to
avoid a fibrotic response that can
lead to an unesthetic result.
Acknowledgments
The study was supported by FIRST-UNIMI
(2007). The authors reported no conflicts of
interest related to this study.
References
1. Paolantonio M. Treatment of gingival
recessions by combined periodontal re-
generative technique, guided tissue re-
generation, and subpedicle connective
tissue graft. A comparative clinical study.
J Periodontol 2002;73:53–62.
2. Oates TW, Robinson M, Gunsolley JC.
Surgical therapies for the treatment of
gingival recession. A systematic review.
Ann Periodontol 2003;8:303–320.
3. Langer B, Calagna L. The subepithelial
connective tissue graft. J Prosthet Dent
1980;44:363–367.
4. Langer B, Langer L. Subepithelial con-
nective tissue graft technique for root
coverage. J Periodontol 1985;56:715–720.
5. Hirsch A, Attal U, Chai E, Goultschin J,
Boyan BD, Schwartz Z. Root coverage
and pocket reduction as combined sur-
gical procedures. J Periodontol 2001;72:
1572–1579.
6. Song JE, Um YJ, Kim CS, et al. Thickness
of posterior palatal masticatory mucosa:
The use of computerized tomography.
J Periodontol 2008;79:406–412.
7. Wara-aswapati N, Pitiphat W, Chandra-
pho N, Rattanayatikul C, Karimbux N.
Thickness of palatal masticatory mu-
cosa associated with age. J Periodontol
2001;72:1407–1412.
The International Journal of Periodontics & Restorative Dentistry
© 2014 BY QUINTESSENCE PUBLISHING CO, INC. PRINTING OF THIS DOCUMENT IS RESTRICTED TO PERSONAL USE ONLY.
NO PART MAY BE REPRODUCED OR TRANSMITTED IN ANY FORM WITHOUT WRITTEN PERMISSION FROM THE PUBLISHER.
8. Jung UW, Um YJ, Choi SH. Histologic
observation of soft tissue acquired from
maxillary tuberosity area for root cover-
age. J Periodontol 2008;79:934–940.
9. Studer SP, Allen EP, Rees TC, Kouba A.
The thickness of masticatory mucosa in
the human hard palate and tuberosity as
potential donor sites for ridge augmen-
tation procedures. J Periodontol 1997;
68:145–151.
10. Arcidiacono A, Ricci G. Clinical and
Histomorphologic Analysis After Ridge
Augmentation Using Connective Tissue
Obtained Either From the Tuber Maxillae
or From the Palate: A One-Year Evalua-
tion [in Italian]. [Proceedings of the XII In-
ternational Congress SIDP, Firenze, Italy].
Florence: SIDP, 2001:57–61.
11. Gagliano N, Moscheni C, Dellavia C, et
al. Morphological and molecular analy-
sis of idiopathic gingival fibromatosis:
A case report. J Clin Periodontol 2005;
32:1116–1121.
12. Gagliano N, Moscheni C, Dellavia C,
et al. Effect of cyclosporin A on human
gingival fibroblast collagen turnover in
relation to the development of gingival
overgrowth: An in vitro study. Biomed
Pharmacother 2004;58:231–238.
13. Muller HP, Schaller N, Eger T, Heinecke
A. Thickness of masticatory mucosa.
J Clin Periodontol 2000;27:431–436.
14. Lee YJ, Kwon YH, Park JB, et al. Epitheli-
al thickness of the palatal mucosa: A his-
tomorphometric study in Koreans. Anat
Rec 2010;293:1966–1970.
15. Soehren SE, Allen AL, Cutright DE, Seib-
ert JS. Clinical and histologic studies of
donor tissues utilized for free grafts of
masticatory mucosa. J Periodontol 1973;
44:727–741.
16. Muller HP, Heinecke A, Schaller N, Eger
T. Masticatory mucosa in subjects with
different periodontal phenotypes. J Clin
Periodontol 2000;27:621–626.
17. Seguier S, Godeau G, Brousse N. Col-
lagen fibers and inflammatory cells in
healthy and diseased human gingival
tissues: A comparative and quantitative
study by immunohistochemistry and au-
tomated image analysis. J Periodontol
2000;71:1079–1085.
18. Seguier S, Godeau G, Brousse N. Immu-
nohistological and morphometric analy-
sis of intra-epithelial lymphocytes and
Langerhans cells in healthy and diseased
human gingival tissues. Arch Oral Biol
2000;45:441–452.
19. Ejeil AL, Gaultier F, Igondjo-Tchen S,
et al. Are cytokines linked to collagen
breakdown during periodontal disease
progression? J Periodontol 2003;74:
196–201.
20. Ejeil AL, Igondjo-Tchen S, Ghomrasseni
S, Pellat B, Godeau G, Gogly B. Expres-
sion of matrix metalloproteinases (MMPs)
and tissue inhibitors of metalloprotein-
ases (TIMPs) in healthy and diseased
human gingiva. J Periodontol 2003;74:
188–195.
21. Walker LC, Overstreet MA, Yeowell HN.
Tissue-specific expression and regula-
tion of the alternatively-spliced forms of
lysyl hydroxylase 2 (LH2) in human kid-
ney cells and skin fibroblasts. Matrix Biol
2005;23:515–523.
22. Van der Slot AJ, Zuurmond AM, van den
Bogaerdt AJ, et al. Increased formation
of pyridinoline cross-links due to higher
telopeptide lysyl hydroxylase levels is
a general fibrotic phenomenon. Matrix
Biol 2004;23:251–257.
23. Kagan H. Characterization and regula-
tion of lysyl oxidase. In: Mecham R (ed).
Biology and Regulation of Extracellular
Matrix: A Series. Regulation of Matrix
Accumulation, vol 1. Orlando: Academ-
ic, 1986:321–398.
24. Sakai T, Gross J. Some properties of the
products of reaction of tadpole collage-
nase with collagen. Biochemistry 1967;
6:518–528.
25. Woessner JF Jr. Matrix metalloproteinas-
es and their inhibitors in connective tissue
remodeling. FASEB J 1991;5:2145–2154.
26. Phipps RP, Borrello MA, Blieden TM. Fi-
broblast heterogeneity in the periodon-
tium and other tissues. J Periodontal Res
1997;32:159–165.
27. Tipton DA, Stricklin GP, Dabbous MK.
Fibroblast heterogeneity in collageno-
lytic response to cyclosporine. J Cell Bio-
chem 1991;46:152–165.
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