Tumor necrosis factor-α converting enzyme (TACE) increases RANKL expression in osteoblasts and serves as a potential biomarker of periodontitis

Lee, Ji Hyun; Choi, Young Jin; Heo, Sun Hee; Lee, Jae Mok; Cho, Je Yoel

doi:10.5483/bmbrep.2011.44.7.473

Cited by 17 publications

(11 citation statements)

References 16 publications

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“…Compared to health, a similar trend of elevated TACE levels was observed in both gingival tissue and GCF (respectively: 1.7‐fold in gingivitis, 2.6‐ and 1.8‐fold in moderate CP, 2.3‐ and 1.5‐fold in severe CP) (Lee et al. ). By studying a group of CP patients who were under treatment with immunosuppressants, it was also deduced that T‐cells are the likely source of this enzyme in the diseased periodontium (Bostanci et al.…”

Section: Review Of Current Literaturementioning

confidence: 64%

The RANKL‐OPG system in clinical periodontology

Belibasakis

Bostancı

2011

J Clinic Periodontology

283

266

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Background and Objectives: The receptor activator of NF-jB ligand-osteoprotegerin (RANKL-OPG) bi-molecular system is the "bottle-neck" regulator of osteoclastogenesis and bone resorption, both in physiological and pathological conditions. This review aims to elaborate the current knowledge on RANKL and OPG in periodontal disease, and to evaluate their diagnostic and prognostic potential as biomarkers of the disease. Materials and Methods: To pursue this aim, electronic and manual searches were performed for identifying clinical and in vivo studies on RANKL and OPG in gingival tissue, gingival crevicular fluid, saliva and blood. Smoking and diabetes mellitus were also considered for their potential effects. Results: Papers fulfilling the inclusion criteria demonstrate that RANKL is upregulated, whereas OPG is down-regulated in periodontitis, compared to periodontal health, resulting in an increased RANKL/OPG ratio. This ratio is further up-regulated in smokers and diabetics, and is not affected by conventional periodontal treatment. Conclusions: The increased RANKL/OPG ratio may serve as a biomarker that denotes the occurrence of periodontitis, but may not necessarily predict on-going disease activity. Its steadily elevated levels post treatment may indicate that the molecular mechanisms of bone resorption are still active, holding an imminent risk for relapse of the disease. Additional adjunct treatment modalities that would "switch-off" the RANKL/OPG ratio may therefore be required.

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Section: Review Of Current Literaturementioning

confidence: 64%

The RANKL‐OPG system in clinical periodontology

Belibasakis

Bostancı

2011

J Clinic Periodontology

283

266

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“…The result were obtained from present experiments were limited to in vitro and ex vivo assays; nevertheless, all outcomes clearly indicated that osteoclastogenic cytokines, in particular sRANKL and TNF-α, are released from lymphocytes by TACE-mediated cleavage and can activate osteoclast precursors to induce osteoclastogenesis from a site distant from the alveolar bone surface in the periodontitis lesion. On the other hand, a study reported that recombinant TACE can promote the production of RANKL from human osteoblast cell line (MG63) in vitro (56), suggesting that osteoblasts may also be engaged in secretion of sRANKL by means of TACE-mediated cleaving of mRANKL expressed on the osteoblasts. Further studies are required to elucidate molecular and cellular mechanisms underlying the production of sRANKL in the context of periodontitis.…”

Section: Discussionmentioning

confidence: 99%

Soluble RANKL Cleaved from Activated Lymphocytes by TNF-α–Converting Enzyme Contributes to Osteoclastogenesis in Periodontitis

Kanzaki

Makihira

Suzuki

et al. 2016

The Journal of Immunology

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Host immune responses play a key role in promoting bone resorption in periodontitis via RANKL-dependent osteoclastogenesis. Both membrane-bound RANKL (mRANKL) expressed on lymphocytes and soluble RANKL (sRANKL) are found in periodontal lesions. However, the underlying mechanism and cellular source of sRANKL release and its biological role in periodontitis are unclear. Tumor necrosis factor-α-converting enzyme (TACE) is reported to cleave 1) precursor TNF-α with release of mature, soluble TNF-α (sTNF-α) and 2) mRANKL with release of sRANKL. Both sTNF-α and sRANKL are found in the periodontitis lesion, leading to the hypothesis that TACE expressed on lymphocytes is engaged in RANKL shedding and that the resulting sRANKL induces osteoclastogenesis. In the present study, upon stimulating peripheral blood lymphocytes (PBLs) with mitogens in vitro, RANKL expression, sRANKL secretion, and TACE expression were all upregulated. Among the four putative mRANKL sheddases examined in neutralization assays, TACE was the only functional sheddase able to cleave mRANKL expressed on PBL. Moreover, PBL culture supernatant stimulated with mitogens in the presence of anti-TACE-antibody or anti-RANKL-antibody showed a marked reduction of osteoclastogenesis from osteoclast precursors, indicating that TACE-mediated sRANKL may possess sufficient osteoclastogenic activity. According to double-color confocal microscopy, B cells expressed a more pronounced level of RANKL and TACE expression than T cells or monocytes in periodontally diseased gingiva. Conditioned medium of patients’ gingival lymphocyte culture increased in vitro osteoclastogenic activity, which was suppressed by the addition of anti-TACE-antibody and anti-RANKL-antibody. Therefore, TACE-mediated cleavage of sRANKL from activated lymphocytes, especially B cells, can promote osteoclastogenesis in periodontitis.

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“…In patients with periodontal disease, TACE protein levels from gingival crevicular fluid were increased in groups with periodontitis (24). In addition, TACE increased RANKL protein expression and decreased OPG in osteoblasts favoring the progression of periodontitis (25). Besides, B cells have been shown to be the major cellular source of TACE and these activated lymphocytes play a key role on the conversion of membrane-coupled RANKL to generate soluble RANKL (15).…”

Section: Discussionmentioning

confidence: 99%

DC-STAMP and TACE Levels are Higher in Patients with Periodontitis

et al. 2020

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Abstract Although periodontitis is one of the commonest infectious inflammatory diseases in humans, the mechanisms involved with its immunopathology remain ill understood. Numerous molecules may induce inflammation and lead to bone resorption, secondary to activation of monocytes into osteoclasts. TACE (TNF-α converting enzyme) and DC-STAMP (dendritic cell-specific transmembrane protein) appear to play a role on bone resorption since TACE induces the release of sRANKL (soluble receptor activator of nuclear factor kappa-β ligand) whereas DC-STAMP is a key factor in osteoclast induction. The present study evaluated the levels of TACE and DC-STAMP in patients with and without periodontitis. Twenty individuals were selected: 10 periodontally healthy participants undergoing gingivectomy for esthetic reasons and 10 diagnosed with periodontitis. Protein levels of such molecules in gingival tissue were established using Western blotting. Protein levels of both TACE and DC-STAMP were higher in the periodontitis group than in the control group (p<0.05; Student t-test). In conclusion, TACE and DC-STAMP protein levels are elevated in patients with periodontitis, favoring progression of bone resorption.

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Tumor necrosis factor-α converting enzyme (TACE) increases RANKL expression in osteoblasts and serves as a potential biomarker of periodontitis

Cited by 17 publications

References 16 publications

The RANKL‐OPG system in clinical periodontology

The RANKL‐OPG system in clinical periodontology

Soluble RANKL Cleaved from Activated Lymphocytes by TNF-α–Converting Enzyme Contributes to Osteoclastogenesis in Periodontitis

DC-STAMP and TACE Levels are Higher in Patients with Periodontitis

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