Co esponding au ho : Rina Su jia i
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Molecula Docking o Sodium Fluo ide o Bioma ke s o Os eogenesis,
Os eoclas ogenesis, and In lamma ion in O odhon ic Too h Mo emen
Rina Su jia i 1, *, Pudji As u i 2, I Dewa Ayu Susilawa i 2, Dyah Se yo ini 3, E na Sulis yani 4 , Melok A is
Wahyukunda i 5, Iin Eliana 4, Vanda Ramadhani 1 and In an Be lian y 6
1 Depa men o O hodon ics, Facul y o Den is y, Uni e si y o Jembe , Indonesia.
2 Depa men o Den is y-Biomedical Science, O al Pa hology, and Maxillo acial, Facul y o Den is y, Uni e si y o Jembe ,
Indonesia.
3 Depa men o Pedodon ics, Facul y o Den is y, Uni e si y o Jembe , Indonesia.
4 Depa men o O al Medicine, Facul y o Den is y, Uni e si y o Jembe , Indonesia.
5 Depa men o Pe iodon ics, Facul y o Den is y, Uni e si y o Jembe , Indonesia.
6 Facul y o Den is y, Uni e si y o Jembe , Indonesia.
Wo ld Jou nal o Ad anced Resea ch and Re iews, 2025, 27(02), 1208-1214
Publica ion his o y: Recei ed on 06 July 2025; e ised on 14 Augus 2025; accep ed on 16 Augus 2025
A icle DOI: h ps://doi.o g/10.30574/wja .2025.27.2.2957
Abs ac
The al eola bone emodeling sys em can inc ease he apposi ion p ocess and educe excessi e al eola bone
eso p ion, which is a ma e ial con aining Fluo ine. Based on he in i o esea ch ha has been conduc ed by adding
Sodium Fluo ide opical adminis a ion a a dose o 11.75 ppm, i can a ec he exp ession o TGF β, RUNX 2, SOX 2,
ALP, Collagen ype 1, OPG, RANKL, IL-10, IL-1β, TNF α on O hodon ic oo h mo emen . Howe e , o see he in e ac ion
be ween he Sodium Fluo ide compound and he abo e bioma ke s, namely Os eogenesis (TGF β, RUNX 2, SOX 2, ALP,
Collagen ype), Os eoclas ogenesis (OPG, RANKL), and in lamma ion (IL-10, IL-1β, TNF α) has no been done. One o he
ways o analyze he in e ac ion is by using in silico es ing, especially using molecula docking. Pu pose: The pu pose o
he s udy is o analyze he Molecula Docking o Sodium Fluo ide o Bioma ke s o Os eogenesis, Os eoclas ogenesis,
and in lamma ion in O hodon ic Too h Mo emen . Ma e ial and me hods: This s udy is a non-expe imen al analy ical
desc ip i e s udy based on chemical compu a ion using compu e de ices h ough an in silico es , especially using
molecula docking. Ligand p epa a ion begins wi h making a wo-dimensional (2D) s uc u e using he Chem D aw
Ul a 8.0 p og am in he Chem O ice 8.0 p og am package, ollowed by a h ee-dimensional (3D) ligand s uc u e made
using Chem3D 8.0 in he Chem O ice 8.0 p og am package and sa ed in a ile o ma . The 3D c ys al s uc u es o TGF
β, RUNX 2, SOX 2, ALP, Collagen ype β, OPG, RANKL, IL-10, IL-1β, and TNF α we e ob ained om he RCSB P o ein Da a
Bank (PDB). Conclusion: Molecula docking analysis showed ha sodium luo ide had low binding a ini y (–1.3 o –
1.8 kcal/mol) o all a ge p o eins, sugges ing weak molecula in e ac ions.
Keywo ds: Molecula docking; In silico es ; Binding a ini y; Os eogenesis; Os eoclas ogenesis
1. In oduc ion
Tee h ha a e mo ed o hodon ically will expe ience a p ocess called bone emodeling, which is a sys em o main ain
he balance o oo h-suppo ing issue, which aims o main ain bone hickness and main ain he ela ionship be ween
ee h and al eola bone so ha i is ela i ely cons an [1]. One o he ma e ials ha can a ec he al eola bone
emodeling sys em, namely, i can inc ease he apposi ion p ocess and can educe excessi e al eola bone eso p ion,
is a ma e ial con aining Fluo ide. In in i o esea ch, Sodium Fluo ide, acco ding o esea ch conduc ed by Su jia i,
concluded ha opical adminis a ion o Sodium Fluo ide a a dose o 11.75 ppm can inc ease he exp ession o TGF β,
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RUNX 2, SOX 2, ALP, collagen ype 1, OPG, RANKL, IL-10, IL-1β, TNF α in o hodon ic oo h mo emen [2]. Howe e , he
ela ionship be ween Sodium Fluo ide compounds and hese bioma ke s has no been explo ed. One way o analyze he
ela ionship o he in e ac ion is by using he in silico es , especially using molecula docking. In gene al, he e m in
silico is used o desc ibe expe imen s conduc ed wi h he help o a compu e . This in silico es can be used o de e mine
he in e ac ion be ween a compound and a a ge molecule, one o which is a ecep o . The in e ac ion can be seen in
he o m and s eng h o he bond h ough molecula docking. The in e ac ion o compounds wi h ecep o s can be
isualized using compu a ional me hods and can be used o de e mine he pha macopho e o a compound.
Based on he desc ip ion abo e, he o mula ion o he p oblem is how he molecula docking o Sodium Fluo ide a ec s
bioma ke s o os eogenesis, os eoclas ogenesis, and in lamma ion in o hodon ic oo h mo emen . The bene i s o he
s udy a e o p o ide basic scien i ic in o ma ion abou he molecula docking o Sodium Fluo ide o bioma ke s o
os eogenesis, os eoclas ogenesis, and in lamma ion in o hodon ic oo h mo emen .
2. Ma e ial and me hods
This s udy is a non-expe imen al analy ical desc ip i e s udy based on chemical compu a ion using compu e de ices
h ough in silico es s. Ligand p epa a ion begins wi h c ea ing a wo-dimensional (2D) s uc u e using he Chem D aw
Ul a 8.0 p og am in he Chem O ice 8.0 p og am package, ollowed by a h ee-dimensional (3D) s uc u e sa ed in a
ile o ma . The 3D c ys al s uc u es o TGF β, RUNX 2, SOX 2, ALP, Collagen ype, OPG, RANKL, IL-10, IL-1β, and TNF α
we e ob ained om he RCSB P o ein Da a Bank (PDB). Each new compound can be p edic ed based on he simila i y
o unc ional g oups o o he compounds ha ha e known po en ial. P edic ion o a ge p o ein, compounds whose
s uc u e and po en ial a e known, can be p edic ed o a ge p o eins in cells. Then molecula docking was pe o med.
Da a analysis esul s om molecula docking in he o m o binding a ini y and isualiza ion.
3. Resul s
In his s udy, Sodium Fluo ide was used as a ligand, and molecula docking was pe o med wi h he a ge p o eins TGF
β, RUNX 2, SOX 2, ALP, collagen ype 1, OPG, RANKL, IL-10, IL-1β, and TNF α. Molecula docking was pe o med using
Pymol and Py x. Be o e docking, a g id box consis ing o a g id cen e and molecula docking dimensions was c ea ed
o each p o ein. The g id box was c ea ed o co e he ligand- ecep o binding as a alida ion o he docking. The g id
box c ea ion da a consis ed o spacing in angs om uni s (x, y, and z) and g id box cen e alues (x, y, and z). In molecula
docking, he pa ame e s analyzed included binding a ini y and isualiza ion.
Binding a ini y is a alue ha indica es he abili y o a ligand o bind o a ecep o . The highe he binding a ini y alue,
he lowe he abili y o he ligand o bind o he ecep o , while a mo e nega i e binding a ini y alue means ha he
ligand and p o ein bind e y s ongly wi hou equi ing a la ge amoun o ene gy (Al Huda e al., 2020).
Table 1 Binding a ini y molecula docking
P o ein
Ligand
Binding A ini y
TGF-β (1PY5)
4-(3-py idin-2-yl-1h-py azol-4-yl)
-9.6
Sodium Fluo ide
-1.5
RUNX 2 (6VGE)
Dexame hasone
-7.9
Sodium Fluo ide
-1.7
SOX 2 (6WX8)
Sulindac
-7.7
Sodium Fluo ide
-1.6
ALP (1ZED)
Dexame hasone
-7.6
Sodium Fluo ide
-1.5
KOLAGEN TIPE 1 (6LOS)
T anilas
-6.1
Sodium Fluo ide
-1.4
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OPG (3URF)
Raloxi ene
-8.4
Sodium Fluo ide
-1.6
RANKL
(5BNQ)
Res e a ol
-7.1
Sodium Fluo ide
-1.3
RANKL (3URF)
Res e a ol
-6.3
Sodium Fluo ide
-1.6
IL-10 (6X93)
Rocaglamide
-6.3
Sodium Fluo ide
-1.4
IL-1β (1ITB)
Res e a ol
-7.7
Sodium Fluo ide
-1.8
IL-1R (1GOY)
Res e a ol
-7.2
Sodium Fluo ide
-1.6
TNF-α (TNFR1) (1EXT)
Res e a ol
-6.9
Sodium Fluo ide
-1.6
Based on he molecula docking esul s be ween Sodium Fluo ide and a ious p o eins in ol ed in os eogenesis and
in lamma ion, i was ound ha Sodium Fluo ide exhibi s ela i ely weak binding a ini y compa ed o o he e e ence
ligands. In gene al, he binding ene gy o Sodium Fluo ide agains all a ge p o eins anged om –1.3 o –1.8 kcal/mol,
indica ing weak in e ac ions be ween sodium luo ide and he a ge p o eins.
On he o he hand, con ol ligands such as dexame hasone, es e a ol, sulindac, aloxi ene, and o he s showed s onge
(mo e nega i e) binding a ini ies. Dexame hasone exhibi ed s ong in e ac ions wi h RUNX2 (–7.9 kcal/mol) and ALP
(–7.6 kcal/mol); es e a ol demons a ed high a ini y o IL-1β (–7.7 kcal/mol), IL-1R (–7.2 kcal/mol), and RANKL (–
7.1 kcal/mol); while sulindac showed s ong in e ac ion wi h SOX2 (–7.7 kcal/mol). No ably, TGF-β exhibi ed he
s onges in e ac ion wi h he ligand 4-(3-py idin-2-yl-1H-py azol-4-yl), wi h a binding a ini y o –9.6 kcal/mol, making
i he s onges in e ac ion eco ded.
ALP – Sodium Fluo ide
Kolagenase 1 – Sodium Fluo ide
IL-1B – Sodium Fluo ide
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IL10 – Sodium Fluo ide
OPG – Sodium Fluo ide
RANKL – Sodium Fluo ide
RANK – Sodium Fluo ide
RUNX2 – Sodium Fluo ide
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SOX2 – Sodium Fluo ide
TGFB – Sodium Fluo ide
TNFR – Sodium Fluo ide
Figu e 1 Visualiza ion molecula docking be ween Sodium Fluo ide ligands and a ge p o ein ecep o s TGF β, RUNX
2, SOX 2, ALP, Collagen ype 1, OPG, RANKL, IL-10, IL-1β, TNF α
4. Discussion
Molecula docking analysis e ealed ha Sodium Fluo ide exhibi s ela i ely low binding a ini y owa d all a ge
p o eins, anging om –1.3 o –1.8 kcal/mol, indica ing weak in e ac ions. In con as , con ol ligands such as
dexame hasone, es e a ol, sulindac, and aloxi ene demons a ed signi ican ly s onge a ini ies (mo e nega i e
alues). Fo ins ance, dexame hasone showed s ong binding o RUNX2 (–7.9 kcal/mol) and ALP (–7.6 kcal/mol), while
es e a ol exhibi ed high a ini y owa d IL-1β (–7.7 kcal/mol), IL-1R (–7.2 kcal/mol), and RANKL (–7.1 kcal/mol). The
s onges in e ac ion was obse ed be ween TGF-β and he ligand 4-(3-py idin-2-yl-1H-py azol-4-yl) wi h a binding
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ene gy o –9.6 kcal/mol. These indings align wi h p e ious s udies showing ha ligands such as es e a ol can s ongly
bind o in lamma o y and os eogenic p o eins, such as RANKL (–6.9 o –7.6 kcal/mol) and IL-1β (–7.7 kcal/mol), as
epo ed in molecula docking and expe imen al s udies [3]. Addi ionally, ano he s udy by Pa il (2024) suppo s ha
es e a ol o ms s ong hyd ogen bonds wi h TNF-α, unde pinning i s po en ial as an an i-in lamma o y and
os eop o ec i e agen [4]. These esul s sugges ha he di ec in e ac ion be ween Sodium Fluo ide and he a ge
p o eins is likely o be molecula ly insigni ican , whe eas con ol ligands wi h s onge binding a ini ies may possess
g ea e po en ial o modula ing biological ac i i ies. This suppo s he hypo hesis ha he biological mechanism o
Sodium Fluo ide may occu indi ec ly o h ough seconda y signaling pa hways, in con as o ligands like
dexame hasone o es e a ol, which show po en ial as biocompa ible and os eop o ec i e agen s.
Based on he esul s o molecula docking, suppo ed by p e ious esea ch s a ing ha Sakallioğlu p o ed ha high
dose Fluo ide adminis a ion can cause an inc ease in TGF-β 1 and TIMP/MMP and an a e age o TIMP/TGF-β 1 [5, 6].
The molecula biological mechanism in mechanical p essu e ecei ed by ee h in o hodon ic ea men is cha ac e ized
by he p esence o an in lamma o y p ocess in he pe iodon al issue. O hodon ic ea men is done by applying
p essu e o he ee h, which causes oo h mo emen in he al eola bone a ound he ee h. Al eola bone emodeling is
e y impo an because i is a p ocess o main aining he balance o he oo h suppo issue. The emodeling p ocess is
used o main ain bone hickness and main ain he ela ionship be ween he oo h and he al eola bone so ha i is
ela i ely cons an [7, 8]. One way o p e en elapse is by e en ion. Re en ion is main aining he mo emen o new
ee h in ha posi ion long enough o s abilize he co ec ion [9]. P essu e on he oo h c own will be ansmi ed
h ough he oo h oo o he al eola bone and pe iodon al ligamen . The su ace o he al eola bone ha is unde
p essu e will unde go a eso p ion p ocess, and he opposi e side will expe ience a pulling o apposi ion p ocess [2].
In lamma o y media o s will igge biological p ocesses ela ed o al eola bone eso p ion and apposi ion. The
biological mechanism ha s imula es al eola bone eso p ion is physiologically ela ed o cy okines.
Cy okines a e a g oup o media o s o issue damage and play a ole in o hodon ic oo h mo emen [10, 11]. Mechanical
p essu e also ac i a es in lamma o y cells, especially mac ophages and neu ophils, o p oduce a ious chemical
media o s, including: P os aglandin, In e leukin-1, In e leukin-6, umo nec osis ac o -alpha, and os eoclas
di e en ia ion by nuclea ac o kappa B ligand ac i a o ecep o and os eop o ege in, which can be iden i ied in
gingi al c e icula luid examina ion. Fu he mo e, mechanical p essu e s imula es al eola bone eso p ion [12, 13].
Bone eso p ion is cha ac e ized by inc eased os eoclas ac i i y con olled by cy okines, namely IL-1, IL-6, and TNF-λ,
which s imula e os eoclas ogenesis in bone eso p ion h ough NF-kβ ligand ac i a o ecep o (RANKL), NF-kβ RANK),
and os eop o ege in (OPG) [14, 15]. Recen s udies ha e shown ha OPG is a RANKL inhibi o and inhibi s he binding
be ween RANKL and RANK, os eoclas ogenesis. Fac o s ha in luence he occu ence o elapse a e bone eso p ion,
which expe iences he ini ial oo h mo emen nine imes g ea e han he apposi ional bone, allowing o g ea e
elapse [16, 17]. To imp o e he apposi ion p ocess by inc easing os eoblas cell p oli e a ion, Fluo ide is gi en.
5. Conclusion
Molecula docking on TGF β, RUNX 2, SOX 2, ALP, Collagen ype 1, OPG, RANKL, IL-10, IL-1β, and TNF α p o eins shows
he a achmen o Sodium Fluo ide o he ac i e side o he p o ein.
Compliance wi h e hical s anda ds
Acknowledgmen s
This s udy was suppo ed by an in e nal g an om he Uni e si y o Jembe .
Disclosu e o con lic o in e es
The au ho s decla e ha he e is no con lic o in e es ega ding he publica ion o his a icle.
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