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Fig. 5. Anti-RANKL and anti-RANKL+miR-146a treatme...

Fig. 5. Anti-RANKL and anti-RANKL+miR-146a treatments decreased gingival mRNA expression of TNF-α and RANKL with different patterns in experimental peri-implantitis of WT and TLR2/4 KO mice. Gingival tissues around ligatured implants and non-ligation implants were excised and processed for RT-qPCR analysis to determine mRNA level of TNF-α of WT mice (a) and TLR2/4 KO mice (b) (mean ± SD, n = ...

Fig. 4. Anti-RANKL and anti-RANKL+miR-146a treatme...

Fig. 4. Anti-RANKL and anti-RANKL+miR-146a treatments decreased the inflammatory cell infiltration of the implant gingival tissues with different patterns in experimental peri-implantitis of WT and TLR2/4 KO mice. HE staining of the gingival tissue around implants were performed in the control group, ligation group, ligation with anti-RANKL antibody treatment group, and ligation with anti-RANKL ...

Fig. 3. Anti-RANKL and anti-RANKL+miR-146a treatme...

Fig. 3. Anti-RANKL and anti-RANKL+miR-146a treatments decreased TRAP-positive cell quantities with different patterns in experimental peri-implantitis of WT and TLR2/4 KO mice. TRAP-positive cells (red color) with 3 or more nuclei were considered osteoclasts and were shown in the control group, ligation group, ligation with anti-RANKL antibody treatment group, and ligation with anti-RANKL antibo...

Fig. 2. Anti-RANKL and anti-RANKL+miR-146a treatme...

Fig. 2. Anti-RANKL and anti-RANKL+miR-146a treatments decreased ligature-induced bone resorption with different patterns in experimental peri-implantitis of WT and TLR2/4 KO mice. Buccal side images of the defleshed skulls were taken of the control (non-ligation) group, ligation (non-treatment) group, ligation with anti-RANKL antibody (ligation+AR) treatment group, and ligation with anti-RANKL a...

Fig. 1. Mouse model of ligature-induced experiment...

Fig. 1. Mouse model of ligature-induced experimental peri-implantitis. (a) Tooth extraction: left maxillary first and second molars extracted at 4 weeks old and the tooth extraction socket healed well with smooth gingiva surface after 6 weeks post-extraction. Implant placement: implant was put in alveolar bone without flap elevation. Ligature placement: at 4 weeks post-implant, 7-0 ligatur...

Table 1 Success rate (SR) of osseointegrated impla...

 Total implantsLostLooseOsseointegratedSuccess rate (%)SR P valueWild type group60654981.670.595TLR2/4 KO group60445286.67Table 1 Success rate (SR) of osseointegrated implants 4 weeks after implant placement

About this article : RANKL blockade alleviates per...

Pan, K., Hu, Y., Wang, Y. et al. RANKL blockade alleviates peri-implant bone loss and is enhanced by anti-inflammatory microRNA-146a through TLR2/4 signaling. Int J Implant Dent 6, 15 (2020). https://doi.org/10.1186/s40729-020-00210-0 Download citation Received: 24 September 2019 Accepted: 12 March 2020 Published: 15 April 2020 DOI: https://doi.org/10.1186/s40729-020-00210-0

Rights and permissions : RANKL blockade alleviates...

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material...

Supplementary information : RANKL blockade allevia...

The numerical data of all graphs.

Additional information : RANKL blockade alleviates...

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Ethics declarations : RANKL blockade alleviates pe...

Not applicable Not applicable Keqing Pan, Yang Hu, Yufeng Wang, Hao Li, Michele Patel, Danyang Wang, Zuomin Wang, and Xiaozhe Han certify that they do not have any commercial or associate interest that represents a conflict of interest in connection with the manuscript. The submitted work was not carried out in the presence of any personal, professional, or financial relationships that could pot...

Author information : RANKL blockade alleviates per...

You can also search for this author in PubMed Google Scholar You can also search for this author in PubMed Google Scholar KP contributed to the conception and design; contributed to the acquisition, analysis, and interpretation of data; and drafted the manuscript. YH contributed to the conception and design, contributed to the acquisition, anal...

Author information : RANKL blockade alleviates per...

Department of Stomatology, The Affiliated Hospital of Qingdao University, College of Stomatology, Qingdao University, Qingdao, 266003, Shandong, China Keqing Pan Department of Immunology and Infectious Diseases, The Forsyth Institute, 245 First Street, Cambridge, MA, 02142, USA Keqing Pan, Yang Hu, Yufeng Wang, Hao Li, Michele Patel & Xiaozhe Han Department of Oral Medicine, Ninth People...

Funding : RANKL blockade alleviates peri-implant b...

This study was supported by NIH NIDCR R01DE025255 and the Forsyth Institute FPILOT36 to X Han and the Forsyth Institute FPILOT52 to Y Hu.

Acknowledgements : RANKL blockade alleviates peri-...

Not applicable

References : RANKL blockade alleviates peri-implan...

Tu S, Zhong D, Xie W, Huang W, Jiang Y, Li Y. Role of toll-like receptor signaling in the pathogenesis of graft-versus-host diseases. Int J Mol Sci. 2016;17(8). Gaddis DE, Michalek SM, Katz J. TLR4 signaling via MyD88 and TRIF differentially shape the CD4+ T cell response to Porphyromonas gingivalis hemagglutinin B. J Immunol. 2011;186(10):5772–83. Zhang P, Liu J, Xu Q, et al. TLR2-dependent m...

References : RANKL blockade alleviates peri-implan...

Kawai T, Akira S. Toll-like receptors and their crosstalk with other innate receptors in infection and immunity. Immunity. 2011;34(5):637–50. Song GG, Kim JH, Lee YH. Toll-like receptor (TLR) and matrix metalloproteinase (MMP) polymorphisms and periodontitis susceptibility: a meta-analysis. Mol Biol Rep. 2013;40(8):5129–41. Lin J, Bi L, Yu X, et al. Porphyromonas gingivalis exacerbates ligat...

References : RANKL blockade alleviates peri-implan...

Shuto T, Wachi T, Shinohara Y, Nikawa H, Makihira S. Increase in receptor activator of nuclear factor kappaB ligand/osteoprotegerin ratio in peri-implant gingiva exposed to Porphyromonas gingivalis lipopolysaccharide. J Dent Sci. 2016;11(1):8–16. O'Connell MB. Prescription drug therapies for prevention and treatment of postmenopausal osteoporosis. J Manag Care Pharm. 2006;12(6 Suppl A):S10-19; ...

References : RANKL blockade alleviates peri-implan...

Bertin TJC, Thivichon-Prince B, LeBlanc ARH, Caldwell MW, Viriot L. Current perspectives on tooth implantation, attachment, and replacement in amniota. Front Physiol. 2018;9:1630. Schminke B, Vom Orde F, Gruber R, Schliephake H, Burgers R, Miosge N. The pathology of bone tissue during peri-implantitis. J Dent Res. 2015;94(2):354–61. Mombelli A, Muller N, Cionca N. The epidemiology of peri-impl...

Abbreviations : RANKL blockade alleviates peri-imp...

Receptor activator of nuclear factor-kappa Β ligand Toll-like receptor Wild type MicroRNA 146a Micro-computed tomography Real-time quantitative PCR Tumor necrosis factor alpha Osteoprotegerin Lipopolysaccharides Hematoxylin and eosin Tartrate-resistant acid phosphatase

Availability of data and materials : RANKL blockad...

Presented in the main paper

Conclusions : RANKL blockade alleviates peri-impla...

In summary, the present study suggests that anti-inflammatory miR-146a enhance anti-RANKL-induced inhibition of peri-implant bone resorption through the regulation of TLR2/4 signaling and inhibition of TNF-α expression. Combination of regimens antagonizing both osteoclastogenesis and inflammation may become a more effective strategy to ameliorate peri-implantitis bone loss.

Discussion : RANKL blockade alleviates peri-implan...

According to the previous studies, miR-146a was regulated by NF-κB and blockade of miR-146a could decrease TLR4 and NF-κB in human cells [41, 42], suggesting that miR-146a is involved in TLR/NF-κB signaling pathway. Our recent study showed that miR-146a inhibited inflammatory cytokine secretion in B cells after challenged with P. gingivalis LPS and decreased bone resorption in experimental peri...

Discussion : RANKL blockade alleviates peri-implan...

Our present study showed that anti-RANKL antibody can significantly inhibit the bone loss in peri-implantitis and additional miR-146a treatment will enhance this inhibition through its anti-inflammation effects via TLR2/4 signaling. This is the first report in a murine model of peri-implantitis to demonstrate that anti-RANKL antibody and miR-146a together can significantly reduce bone resorption a...

Results : RANKL blockade alleviates peri-implant b...

In both WT mice and TLR2/4 KO mice, a significantly higher number of inflammatory cells were found infiltrating around the peri-implant tissues in the ligation group compared with the non-ligation group (Fig. 4a–c). However, the number of inflammatory cells in tissues of the ligation group was not significantly changed when treated with anti-RANKL antibody alone in both WT and TLR2/4 KO mice com...

Results : RANKL blockade alleviates peri-implant b...

In our ligature-induced experimental peri-implantitis mouse model, teeth extraction, implant placement, ligation placement, and gingival injection will be performed in a 12-week process (Fig. 1). 86.67% (52 out of 60) of implants in TLR2/4 KO mice achieved osteointegration (no mobility when touched by needles, no obvious bleeding upon probing) after being placed for 4 weeks, which has no signifi...

Methods : RANKL blockade alleviates peri-implant b...

Palatal gingival tissues were isolated from around ligatured implants and were homogenized in lysis buffer using a tissue homogenizer. Total RNA was extracted using PureLink® RNA Mini Kit (Ambion). cDNA was synthesized using the SuperScript III Reversed Transcriptase kit (Invitrogen) according to the manufacturer’s protocol. The mRNA expression of TNF-α and RANKL in gingival was determined by ...

Methods : RANKL blockade alleviates peri-implant b...

The ligations were maintained for 2 weeks, and after which the mice were euthanized by CO2 inhalation and the maxilla were harvested. The gingival tissues of half group of mice were isolated and collected for mRNA expression study. The skulls left were defleshed by beetles for 1 week. Briefly, in beetle’s chamber, freshly dissected skull was put in a paper cup with 0.5 cm diameter holes at...

Methods : RANKL blockade alleviates peri-implant b...

Wild-type (WT) C57BL/6 and TLR2 KO and TLR4 KO mice in C57/BL6 background were purchased from the Jackson Laboratory (Bar Harbor, ME). TLR2 and TLR4 double KO mice (TLR2/4 KO) were crossbreed from TLR2 KO and TLR4 KO mice and confirmed by genotyping. All the animal-associated protocols were reviewed and approved (#17-022) by the Institutional Animal Care and Use Committee of the Forsyth Institute....

Background : RANKL blockade alleviates peri-implan...

Toll-like receptors (TLR) are a family of well-characterized pattern recognition receptors (PRRs) and play an important role in the induction of pro-inflammatory cytokines by recognizing the signature molecules of the host innate immunity [25,26,27]. Our previous studies showed that TLR2 are associated with implant bone loss in a mouse model of peri-implantitis [5] and TLR4 is essential for period...

Background : RANKL blockade alleviates peri-implan...

Dental implant has become a preferable choice to restore the missing tooth in the past few decades for functional and esthetic purposes [1]. However, peri-implantitis has become prevalent accompanying the exponential growth of dental implant procedures [2, 3]. Peri-implantitis is indicated by infection of implant surrounding soft tissues and bone loss, resulting in implant failure eventually [4,5,...

Abstract : RANKL blockade alleviates peri-implant ...

This study suggests that anti-inflammatory miR-146a enhance anti-RANKL-induced inhibition of peri-implant bone resorption through the regulation of TLR2/4 signaling and inhibition of TNF-α expression.

Abstract : RANKL blockade alleviates peri-implant ...

The present study was to determine the effect of local anti-RANKL antibody administration in the presence or absence of microRNA-146a on ligature-induced peri-implant bone resorption, and the potential role of TLR2/4 signaling in such effect. Titanium implants were placed in the left maxilla alveolar bone 6 weeks after extraction of first and second molars in C57/BL6 wild-type (WT) and TLR2−/...

Fig. 5. Anti-RANKL and anti-RANKL+miR-146a treatme...

Fig. 5. Anti-RANKL and anti-RANKL+miR-146a treatments decreased gingival mRNA expression of TNF-α and RANKL with different patterns in experimental peri-implantitis of WT and TLR2/4 KO mice. Gingival tissues around ligatured implants and non-ligation implants were excised and processed for RT-qPCR analysis to determine mRNA level of TNF-α of WT mice (a) and TLR2/4 KO mice (b) (mean ± SD, n = ...

Fig. 4. Anti-RANKL and anti-RANKL+miR-146a treatme...

Fig. 4. Anti-RANKL and anti-RANKL+miR-146a treatments decreased the inflammatory cell infiltration of the implant gingival tissues with different patterns in experimental peri-implantitis of WT and TLR2/4 KO mice. HE staining of the gingival tissue around implants were performed in the control group, ligation group, ligation with anti-RANKL antibody treatment group, and ligation with anti-RANKL ...

Fig. 3. Anti-RANKL and anti-RANKL+miR-146a treatme...

Fig. 3. Anti-RANKL and anti-RANKL+miR-146a treatments decreased TRAP-positive cell quantities with different patterns in experimental peri-implantitis of WT and TLR2/4 KO mice. TRAP-positive cells (red color) with 3 or more nuclei were considered osteoclasts and were shown in the control group, ligation group, ligation with anti-RANKL antibody treatment group, and ligation with anti-RANKL antibo...

Fig. 2. Anti-RANKL and anti-RANKL+miR-146a treatme...

Fig. 2. Anti-RANKL and anti-RANKL+miR-146a treatments decreased ligature-induced bone resorption with different patterns in experimental peri-implantitis of WT and TLR2/4 KO mice. Buccal side images of the defleshed skulls were taken of the control (non-ligation) group, ligation (non-treatment) group, ligation with anti-RANKL antibody (ligation+AR) treatment group, and ligation with anti-RANKL a...

Fig. 1. Mouse model of ligature-induced experiment...

Fig. 1. Mouse model of ligature-induced experimental peri-implantitis. (a) Tooth extraction: left maxillary first and second molars extracted at 4 weeks old and the tooth extraction socket healed well with smooth gingiva surface after 6 weeks post-extraction. Implant placement: implant was put in alveolar bone without flap elevation. Ligature placement: at 4 weeks post-implant, 7-0 ligatur...

Table 1 Success rate (SR) of osseointegrated impla...

 Total implantsLostLooseOsseointegratedSuccess rate (%)SR P valueWild type group60654981.670.595TLR2/4 KO group60445286.67Table 1 Success rate (SR) of osseointegrated implants 4 weeks after implant placement

About this article : RANKL blockade alleviates per...

Pan, K., Hu, Y., Wang, Y. et al. RANKL blockade alleviates peri-implant bone loss and is enhanced by anti-inflammatory microRNA-146a through TLR2/4 signaling. Int J Implant Dent 6, 15 (2020). https://doi.org/10.1186/s40729-020-00210-0 Download citation Received: 24 September 2019 Accepted: 12 March 2020 Published: 15 April 2020 DOI: https://doi.org/10.1186/s40729-020-00210-0

Rights and permissions : RANKL blockade alleviates...

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material...

Supplementary information : RANKL blockade allevia...

The numerical data of all graphs.

Additional information : RANKL blockade alleviates...

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Ethics declarations : RANKL blockade alleviates pe...

Not applicable Not applicable Keqing Pan, Yang Hu, Yufeng Wang, Hao Li, Michele Patel, Danyang Wang, Zuomin Wang, and Xiaozhe Han certify that they do not have any commercial or associate interest that represents a conflict of interest in connection with the manuscript. The submitted work was not carried out in the presence of any personal, professional, or financial relationships that could pot...

Author information : RANKL blockade alleviates per...

You can also search for this author in PubMed Google Scholar You can also search for this author in PubMed Google Scholar KP contributed to the conception and design; contributed to the acquisition, analysis, and interpretation of data; and drafted the manuscript. YH contributed to the conception and design, contributed to the acquisition, analysis, and interpretation of data; drafted the manu...

Author information : RANKL blockade alleviates per...

Department of Stomatology, The Affiliated Hospital of Qingdao University, College of Stomatology, Qingdao University, Qingdao, 266003, Shandong, China Keqing Pan Department of Immunology and Infectious Diseases, The Forsyth Institute, 245 First Street, Cambridge, MA, 02142, USA Keqing Pan, Yang Hu, Yufeng Wang, Hao Li, Michele Patel & Xiaozhe Han Department of Oral Medicine, Ninth People...

Funding : RANKL blockade alleviates peri-implant b...

This study was supported by NIH NIDCR R01DE025255 and the Forsyth Institute FPILOT36 to X Han and the Forsyth Institute FPILOT52 to Y Hu.

Acknowledgements : RANKL blockade alleviates peri-...

Not applicable

References : RANKL blockade alleviates peri-implan...

Tu S, Zhong D, Xie W, Huang W, Jiang Y, Li Y. Role of toll-like receptor signaling in the pathogenesis of graft-versus-host diseases. Int J Mol Sci. 2016;17(8). Gaddis DE, Michalek SM, Katz J. TLR4 signaling via MyD88 and TRIF differentially shape the CD4+ T cell response to Porphyromonas gingivalis hemagglutinin B. J Immunol. 2011;186(10):5772–83. Zhang P, Liu J, Xu Q, et al. TLR2-dependent m...

References : RANKL blockade alleviates peri-implan...

Kawai T, Akira S. Toll-like receptors and their crosstalk with other innate receptors in infection and immunity. Immunity. 2011;34(5):637–50. Song GG, Kim JH, Lee YH. Toll-like receptor (TLR) and matrix metalloproteinase (MMP) polymorphisms and periodontitis susceptibility: a meta-analysis. Mol Biol Rep. 2013;40(8):5129–41. Lin J, Bi L, Yu X, et al. Porphyromonas gingivalis exacerbates ligat...

References : RANKL blockade alleviates peri-implan...

Shuto T, Wachi T, Shinohara Y, Nikawa H, Makihira S. Increase in receptor activator of nuclear factor kappaB ligand/osteoprotegerin ratio in peri-implant gingiva exposed to Porphyromonas gingivalis lipopolysaccharide. J Dent Sci. 2016;11(1):8–16. O'Connell MB. Prescription drug therapies for prevention and treatment of postmenopausal osteoporosis. J Manag Care Pharm. 2006;12(6 Suppl A):S10-19; ...

References : RANKL blockade alleviates peri-implan...

Bertin TJC, Thivichon-Prince B, LeBlanc ARH, Caldwell MW, Viriot L. Current perspectives on tooth implantation, attachment, and replacement in amniota. Front Physiol. 2018;9:1630. Schminke B, Vom Orde F, Gruber R, Schliephake H, Burgers R, Miosge N. The pathology of bone tissue during peri-implantitis. J Dent Res. 2015;94(2):354–61. Mombelli A, Muller N, Cionca N. The epidemiology of peri-impl...

Abbreviations : RANKL blockade alleviates peri-imp...

Receptor activator of nuclear factor-kappa Β ligand Toll-like receptor Wild type MicroRNA 146a Micro-computed tomography Real-time quantitative PCR Tumor necrosis factor alpha Osteoprotegerin Lipopolysaccharides Hematoxylin and eosin Tartrate-resistant acid phosphatase

Availability of data and materials : RANKL blockad...

Presented in the main paper

Conclusions : RANKL blockade alleviates peri-impla...

In summary, the present study suggests that anti-inflammatory miR-146a enhance anti-RANKL-induced inhibition of peri-implant bone resorption through the regulation of TLR2/4 signaling and inhibition of TNF-α expression. Combination of regimens antagonizing both osteoclastogenesis and inflammation may become a more effective strategy to ameliorate peri-implantitis bone loss.

Discussion : RANKL blockade alleviates peri-implan...

According to the previous studies, miR-146a was regulated by NF-κB and blockade of miR-146a could decrease TLR4 and NF-κB in human cells [41, 42], suggesting that miR-146a is involved in TLR/NF-κB signaling pathway. Our recent study showed that miR-146a inhibited inflammatory cytokine secretion in B cells after challenged with P. gingivalis LPS and decreased bone resorption in experimental peri...

Discussion : RANKL blockade alleviates peri-implan...

Our present study showed that anti-RANKL antibody can significantly inhibit the bone loss in peri-implantitis and additional miR-146a treatment will enhance this inhibition through its anti-inflammation effects via TLR2/4 signaling. This is the first report in a murine model of peri-implantitis to demonstrate that anti-RANKL antibody and miR-146a together can significantly reduce bone resorption a...

Results : RANKL blockade alleviates peri-implant b...

In both WT mice and TLR2/4 KO mice, a significantly higher number of inflammatory cells were found infiltrating around the peri-implant tissues in the ligation group compared with the non-ligation group (Fig. 4a–c). However, the number of inflammatory cells in tissues of the ligation group was not significantly changed when treated with anti-RANKL antibody alone in both WT and TLR2/4 KO mice com...

Results : RANKL blockade alleviates peri-implant b...

In our ligature-induced experimental peri-implantitis mouse model, teeth extraction, implant placement, ligation placement, and gingival injection will be performed in a 12-week process (Fig. 1). 86.67% (52 out of 60) of implants in TLR2/4 KO mice achieved osteointegration (no mobility when touched by needles, no obvious bleeding upon probing) after being placed for 4 weeks, which has no signifi...

Methods : RANKL blockade alleviates peri-implant b...

Palatal gingival tissues were isolated from around ligatured implants and were homogenized in lysis buffer using a tissue homogenizer. Total RNA was extracted using PureLink® RNA Mini Kit (Ambion). cDNA was synthesized using the SuperScript III Reversed Transcriptase kit (Invitrogen) according to the manufacturer’s protocol. The mRNA expression of TNF-α and RANKL in gingival was determined by ...

Methods : RANKL blockade alleviates peri-implant b...

The ligations were maintained for 2 weeks, and after which the mice were euthanized by CO2 inhalation and the maxilla were harvested. The gingival tissues of half group of mice were isolated and collected for mRNA expression study. The skulls left were defleshed by beetles for 1 week. Briefly, in beetle’s chamber, freshly dissected skull was put in a paper cup with 0.5 cm diameter holes at...

Methods : RANKL blockade alleviates peri-implant b...

Wild-type (WT) C57BL/6 and TLR2 KO and TLR4 KO mice in C57/BL6 background were purchased from the Jackson Laboratory (Bar Harbor, ME). TLR2 and TLR4 double KO mice (TLR2/4 KO) were crossbreed from TLR2 KO and TLR4 KO mice and confirmed by genotyping. All the animal-associated protocols were reviewed and approved (#17-022) by the Institutional Animal Care and Use Committee of the Forsyth Institute....

Background : RANKL blockade alleviates peri-implan...

Toll-like receptors (TLR) are a family of well-characterized pattern recognition receptors (PRRs) and play an important role in the induction of pro-inflammatory cytokines by recognizing the signature molecules of the host innate immunity [25,26,27]. Our previous studies showed that TLR2 are associated with implant bone loss in a mouse model of peri-implantitis [5] and TLR4 is essential for period...

Background : RANKL blockade alleviates peri-implan...

Dental implant has become a preferable choice to restore the missing tooth in the past few decades for functional and esthetic purposes [1]. However, peri-implantitis has become prevalent accompanying the exponential growth of dental implant procedures [2, 3]. Peri-implantitis is indicated by infection of implant surrounding soft tissues and bone loss, resulting in implant failure eventually [4,5,...

Abstract : RANKL blockade alleviates peri-implant ...

This study suggests that anti-inflammatory miR-146a enhance anti-RANKL-induced inhibition of peri-implant bone resorption through the regulation of TLR2/4 signaling and inhibition of TNF-α expression.

Abstract : RANKL blockade alleviates peri-implant ...

The present study was to determine the effect of local anti-RANKL antibody administration in the presence or absence of microRNA-146a on ligature-induced peri-implant bone resorption, and the potential role of TLR2/4 signaling in such effect. Titanium implants were placed in the left maxilla alveolar bone 6 weeks after extraction of first and second molars in C57/BL6 wild-type (WT) and TLR2−/...

RANKL: struktur, fungsi, & peran

StrukturStruktur organisasi RANKL sangat mirip dengan anggota family TNF lainnya, yaitu punya domain intrasel yang pendek dan domain ekstrasel yang panjang, dimana ekson pertama mengkodekan domain intrasel, sedangkan ekson tengah dan ekson purna mengkodekan domain ekstraseluler.Faktanya, melalui analisis filogeni family TNF, didapati bahwa RANKL berkaitan erat dengan CD40L dan molekul-molekul ini...

RANKL

RANKL adalah anggota superfamily sitokin TNF (Tumour Necrosis Factor, Faktor Nekrosis/ Kematian Tumor). Para anggota family TNF menjadi perantara bagi beberapa proses biologi. RANKL itu sangat penting dalam tulang, sistem kekebalan tubuh, dan epitel mamari.Analisis promoter RANKL menyingkapkan kehadiran tapak pengikat (binding sites) untuk dua stimulator kuat protein ini, yaitu vitamin D dan glu...