|Year : 2020 | Volume
| Issue : 1 | Page : 33-37
Quantitative analysis of oncostatin M levels in chronic periodontitis patients
Farooque Khan1, Surekha Rathod1, Abhay Kolte1, Madhur Gupta2, Suresh Chari2, Noopur Gonde1
1 Department of Periodontology and Implantology, VSPM Dental College and Research Centre, Nagpur, Maharashtra, India
2 Department of Biochemistry, NKP Salve Institute of Medical Sciences, Nagpur, Maharashtra, India
|Date of Submission||19-Oct-2019|
|Date of Decision||10-Nov-2019|
|Date of Acceptance||04-Dec-2019|
|Date of Web Publication||29-Jul-2020|
Dr. Surekha Rathod
104, Department of Periodontology and Implantology, VSPM Dental College and Research Centre, Nagpur, Maharashtra
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Background: Oncostatin M (OSM) is the cytokine from the family of interleukin-6. Inflammation, tissue turnover, healing, and repair alter the levels of OSM. The present study was aimed to evaluate the gingival crevicular fluid (GCF) and serum OSM levels in clinically healthy, chronic gingivitis and chronic periodontitis (CP) patients and subsequently after nonsurgical periodontal therapy (NSPT). Materials and Methods: Sixty patients were equally divided into four groups as healthy, chronic gingivitis, CP, and CP with NSPT were included in this study. After 6 weeks of initial periodontal therapy the clinical parameters were measured and OSM levels in GCF and serum were assessed by using enzyme linked immunosorbent assay. Results: The levels of OSM in GCF and serum increased significantly with severity of periodontal disease. There was a significant decrease in OSM levels in GCF and serum in CP with NSPT group. Conclusion: GCF and serum OSM levels can be considered as an appropriate biomarker to be correlated with the severity of periodontal disease. Thus, the increased OSM levels suggest its role in the pathogenesis of periodontal disease and prevent systemic complications.
Keywords: Chronic periodontitis, gingival crevicular fluid, oncostatin M, serum
|How to cite this article:|
Khan F, Rathod S, Kolte A, Gupta M, Chari S, Gonde N. Quantitative analysis of oncostatin M levels in chronic periodontitis patients. J Int Clin Dent Res Organ 2020;12:33-7
|How to cite this URL:|
Khan F, Rathod S, Kolte A, Gupta M, Chari S, Gonde N. Quantitative analysis of oncostatin M levels in chronic periodontitis patients. J Int Clin Dent Res Organ [serial online] 2020 [cited 2020 Oct 26];12:33-7. Available from: https://www.jicdro.org/text.asp?2020/12/1/33/291113
| Introduction|| |
Periodontitis is a multifactorial disease affecting the supporting structures of the teeth. Periodontopathogens present in the dental plaque stimulate host immune responses. The severity of periodontal inflammation depends on the complex interaction between periodontopathogens and host immune system. This triggers imbalance between activities of pro-inflammatory and anti-inflammatory mediators., Oncostatin M (OSM) is a 28 kDa glycoprotein produced mainly by activated T-cells, neutrophils, monocytes, and macrophages. It belongs to the interleukin (IL)-6 family of cytokines, which additionally includes ciliary neurotrophic factor, leukemia inhibitory factor, cardiotrophin-1, and IL-11. It was first purified and biochemically characterized on the basis of its anti-proliferative activity on A375 human melanoma cell line in vitro and fulfilled the Koch's postulates., Studies have explored the role of OSM in cartilage metabolism, wound healing, tissue regeneration and repair and in chronic inflammatory conditions including rheumatoid arthritis, chronic obstructive sialadenitis, apical periodontitis, atherosclerosis, and cardiovascular diseases.,,,,,, Thorat et al. found decreased levels of OSM after Phase-I periodontal therapy and concluded that OSM plays a significant role in pathogenesis and progression of periodontal diseases. Role of quantification of gingival crevicular fluid (GCF) levels of OSM, in providing useful information for the diagnosis of periodontal disease status has been evaluated in literature. Hence, this study aimed to estimation of OSM levels in serum and GCF in patients with chronic periodontitis (CP).
| Materials and Methods|| |
A total of 60 patients, ≥35 years of age and affected with CP (28 men and 32 women; age range 20–55 years) visiting the outpatient Department of Periodontology and Implantology between December 2018 and May 2019 were recruited for the study. Periodontitis was classified according to the classification given by Armitage.
These patients were assessed clinically and biochemically. The study protocol was approved by the Institutional Ethics Committee of our institute in accordance with the Helsinki Declaration of 1975 (revised in 2000). A special pro forma was designed so as to have a systematic recording of information and observations which included detailed case history, clinical examination, and periodontal indices and written informed consent of the patients. Prior to the initiation of the study an informed consent was obtained from all the patients who agreed to participate voluntarily.
The study comprised four groups each having 20 patients.
Group I – periodontally healthy group. Group II – chronic gingivitis group with clinical signs of gingival inflammation, probing depth ≤3 mm, and no clinical attachment loss (CAL) in multiple sites. Group III – CP group with probing pocket depth (PPD) ≥5 mm and clinical attachment levels ≥5 mm at multiple sites. Group IV – nonsurgical periodontal therapy (NSPT) group, included patients from Group III after NSPT with follow-up period of 6 weeks.
- Individuals ≥35 years of age
- Individuals diagnosed with CP
- Periodontally healthy controls in Group I
- Individuals with chronic gingivitis in Group II
- Individuals diagnosed with chronic generalized periodontitis in Group III
- Individuals from Group III who received NSPT included in Group IV.
Patients exhibiting the following conditions were excluded from the study:
- Any periodontal treatment or systemic antibiotic therapy in previous 6 months
- Patients who were or had history of smoking
- Pregnant ladies or lactating mothers
- Systemically compromised individuals were excluded from the study.
Assessment of clinical parameters
The clinical parameters were measured by a previously calibrated examiner (FK). Periodontal indices such as plaque index (PI) (Silness and Loe, 1964) and gingival index (GI) (Loe and Silness, 1963) were measured to assess periodontal status. PPD and CAL were recorded at baseline in all the four groups and after 6 weeks in case of Group IV. PPD measurements were performed using a manual periodontal probe from base of pocket to gingival margin to check the improvement after NSPT. Levels of OSM in GCF and serum were assessed in all the groups by using enzyme linked immunosorbent assay (ELISA). While in Group IV the level of OSM in GCF and serum were measured at 6 weeks after NSPT. The patients were instructed for self-performed plaque-control measures. In Group IV, scaling and root planing was performed followed by oral hygiene instruction as NSPT at baseline and at 6 weeks of follow-up.
Collection of gingival crevicular fluid samples
Based on the periodontal status, the site with the deepest pocket was isolated with a cotton roll, air dried, and supragingival plaque was removed without touching the marginal gingiva. Then, the sample was collected from that site. A standardized volume of 3 μl of GCF was collected by placing the microcapillary pipette at the entrance of the gingival sulcus and was immediately transferred to airtight plastic vials to be stored at −70°C until assayed. Those sites which did not express appropriate volume of fluid and micropipettes which were contaminated with blood and saliva were discarded.
Collection of serum samples and biochemical assay
A total of 4 ml of blood was collected from antecubital fossa by venepuncture using a 20-G needle, serum was separated from blood by centrifuging at 300 rpm for 5 min. The extracted serum was immediately transferred to a plastic vial and stored at −80°C until assayed. Samples were assayed by another calibrated examiner (SR) for OSM level using commercially available ELISA kit and were analyzed according to manufacturer's protocol. The primary wavelength of 450 nm was used to read the absorbance of each well. The levels of OSM in both the GCF and serum tested samples were estimated using the standard curve. The investigator was blinded to the groups.
The data on demographic parameters such as age and gender were obtained from each individual. Continuous variables were presented as mean and standard deviation. Clinical parameters and levels of OSM in GCF and serum were compared among the four groups by performing one-way ANOVA and post hoc. Bonferroni t-test was applied for pair–wise comparison. A paired t-test was used to compare levels of OSM in GCF and serum in Groups III and IV. Pearson's correlation coefficient was used to assess the nature and strength of correlation between levels of OSM in GCF and serum with clinical parameters. The level of significance was set at P < 0.05. STATA version 13.1 statistical software, (Nagpur, Maharashtra, India) was used for data analysis.
| Results|| |
The study comprised of total 60 patients divided as 20 patients in Group I (10 males and 10 females); 20 patients in Group II (9 males and 11 females); 20 patients in Group III (9 males and 11 females). The mean age of patients for Group I was 31.0 ± 7.6 years, for Group II was 33.8 ± 7.95 years and for Group III and IV was 38.8 ± 7.8 years. A significantly higher mean PPD, CAL, GI, and PI were also recorded in Group III [Table 1]. Group III showed significantly higher mean levels of OSM in GCF and serum (0.7202 ± 0.14 pg/μl and 0.076 ± 0.01 pg/μl, respectively) as compared to other groups. The mean level of OSM-GCF in Groups I and II was 0.0564 ± 0.02 pg/μl and 0.1838 ± 0.022 pg/μl, respectively. The mean level of OSM-serum in Groups I and II was 0.002 ± 0.001 pg/μl and 0.004 ± 0.0006 pg/μl, respectively [Table 1]. The mean level of OSM in GCF and serum was the highest for Group III and differed significantly from that of Groups I, II, and IV [Table 2] and [Table 3]. In Group III, a significant improvement in the clinical parameters (PPD, CAL, GI, and PI) as well as in mean levels of OSM in GCF and serum was reported after NSPT [Table 4]. The difference in the levels of OSM in GCF and serum between Groups IV and III was found to be statistically significant (P < 0.001) on comparison of by paired t-test [Table 5]. Using Pearson's correlation coefficient test, we also found a positive and highly significant correlation between levels of OSM in GCF and serum OSM [Table 6].
|Table 1: Descriptive statistics of the study population (mean±standard deviation)|
Click here to view
|Table 2: Pairwise comparison of oncostatin M levels in Gingival Crevicular Fluid (GCF) by using post hoc multiple comparison Bonferroni t-test for the four groups|
Click here to view
|Table 3: Pairwise comparison of levels of oncostatin M in Serum by using post hoc multiple comparison Bonferroni t-test for the four groups|
Click here to view
|Table 4: Pearson's correlation coefficient test comparing the levels of oncostatin M in gingival crevicular fluid and serum to clinical parameters (pocket probing defects, clinical attachment level, gingival index, and plaque index) among the groups|
Click here to view
|Table 5: Paired t-test to compare oncostatin M levels in gingival crevicular fluid and serum in Groups III and IV|
Click here to view
|Table 6: Correlation between oncostatin M levels in gingival crevicular fluid and serum using Pearson's correlation coefficient test|
Click here to view
| Discussion|| |
Human OSM is a multifunctional cytokine of the IL-6 subfamily secreted by human T-cells and monocyte lineages as an inflammatory response to bacterial products which may induce prolonged expression of ICAM-1. This modulates leukocyte adhesion and recruitment of large number to inflammatory sites, leading to destruction of periodontium. Thus, low levels of OSM produced at inflammatory sites can play a role in relapsing chronic inflammatory diseases by inappropriate recurrent neutrophil recruitment there. Such studies suggest an enigmatic role of OSM in various biological processes. OSM has emerged as a pleiotropic molecule involved in several physiologic and pathologic conditions including inflammation, bone metabolism, healing, and regeneration.,,
The present study was designed to estimate the levels of OSM in GCF and serum in periodontal health and disease. GCF and serum samples from all the groups were collected at the first visit and 6 weeks after NSPT in Group IV, as most of the inflammation subsides and healing generally by repair over a long period of time. The presence of pro-inflammatory and inflammatory cytokines in GCF and serum has been proposed as potentially useful diagnostic and prognostic markers of periodontal destruction.,
In the present study, the significant increase in levels of OSM in serum of patients with CP can be attributed to the surrounding diseased tissues. The present study reported a significant decrease in the levels of OSM in GCF and serum and clinical parameters after NSPT. Similar reports conducted by Thorat et al. and Lin et al. found a significant increase in the OSM levels in GCF and serum with increased destruction of periodontal tissues and a significant decrease in the OSM levels in GCF and serum following NSPT in CP patients. Their work suggests that OSM has a crucial role in the pathogenesis of periodontal diseases.,
Lu et al. in 2006 found a positive correlation between the OSM levels in the GCF and expression of receptor activator of nuclear factor kappa-B ligand in patients with CP. A statistically nonsignificant difference was found in the levels of OSM in the serum of Group I and Group II. The mean level of serum OSM in Group II was found to be much lower than that in Group III. These variations in the levels of serum OSM suggest that the differences in soft and hard tissue destruction of the periodontium support the role of OSM in inflammation and bone resorption.
In contrast to the results obtained in our study, Palmqvist et al. in an in vitro study was unable to detect the expression of OSM by human gingival fibroblasts under inflammation. Becerik et al. investigated the levels of OSM in GCF and plasma in patients with gingivitis, CP and aggressive periodontitis and found no correlation between the levels of OSM in GCF and plasma in these periodontal diseases. In this present clinico-biochemical study, we found that the mean level of OSM in GCF and serum increased with the severity of the periodontal disease which decreased after NSPT. This indicates a positive effect of the levels of OSM in periodontal disease progression.
| Conclusion|| |
Within the limits of our study, it can be concluded that both GCF and serum OSM levels can be regarded as appropriate biomarker to establish its correlation with periodontal disease severity. Thus, the increased OSM levels suggest its role in the pathogenesis of periodontal disease and prevent systemic complications. However, it is not clear yet whether the elevated levels of GCF and serum OSM are the cause or the consequence of periodontitis. Further longitudinal multicenter prospective studies with larger sample size are needed to clarify the role of OSM in the pathogenesis of periodontitis and to validate OSM as "novel biomarker" of periodontal diseases.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Kinane DF, Lappin DF. Clinical, pathological and immunological aspects of periodontal disease. Acta Odontol Scand 2001;59:154-60.
Honda T, Domon H, Okui T, Kajita K, Amanuma R, Yamazaki K. Balance of inflammatory response in stable gingivitis and progressive periodontitis lesions. Clin Exp Immunol 2006;144:35-40.
Tanaka M, Miyajima A. Oncostatin M, a multifunctional cytokine. Rev Physiol Biochem Pharmacol 2003;149:39-52.
Rose TM, Bruce AG. Oncostatin M is a member of a cytokine family that includes leukemia-inhibitory factor, granulocyte colony-stimulating factor, and interleukin 6. Proc Natl Acad Sci U S A 1991;88:8641-5.
Zarling JM, Shoyab M, Marquardt H, Hanson MB, Lioubin MN, Todaro GJ. Oncostatin M: A growth regulator produced by differentiated histiocytic lymphoma cells. Proc Natl Acad Sci U S A 1986;83:9739-43.
Modur V, Feldhaus MJ, Weyrich AS, Jicha DL, Prescott SM, Zimmerman GA, et al
. Oncostatin M is a proinflammatory mediator. In vivo
effects correlate with endothelial cell expression of inflammatory cytokines and adhesion molecules. J Clin Invest 1997;100:158-68.
Sanchez C, Deberg MA, Burton S, Devel P, Reginster JY, Henrotin YE. Differential regulation of chondrocyte metabolism by oncostatin M and interleukin-6. Osteoarthritis Cartilage 2004;12:801-10.
Shin SH, Han SK, Jeong SH, Kim WK. Potential of oncostatin M to accelerate diabetic wound healing. Int Wound J 2014;11:398-403.
Hohensinner PJ, Kaun C, Rychli K, Niessner A, Pfaffenberger S, Rega G, et al
. The inflammatory mediator oncostatin M induces stromal derived factor-1 in human adult cardiac cells. FASEB J 2009;23:774-82.
Atlev LM, Carlson K, Pietka TA, Eyre DR. Oncostatin M induces collagen degradation in human articular cartilage. Osteoarthritis Cartilage 2001;9 Suppl 2:S12.
Lee HM, Cho JG, Kang HJ, Chae SW, Hwang SJ, Jung KY, et al
. Expression of oncostatin M in chronic obstructive sialadenitis of the submandibular gland. Ann Otol Rhinol Laryngol 2008;117:347-52.
Tsai CH, Huang FM, Chang YC. Immunohistochemical localization of oncostatin M in epithelialized apical periodontitis lesions. Int Endod J 2008;41:772-6.
Bernard C, Merval R, Lebret M, Delerive P, Dusanter-Fourt I, Lehoux S, et al
. Oncostatin M induces interleukin-6 and cyclooxygenase-2 expression in human vascular smooth muscle cells: Synergy with interleukin-1beta. Circ Res 1999;85:1124-31.
Thorat M, Pradeep AR, Garg G. Correlation of levels of oncostatin M cytokine in crevicular fluid and serum in periodontal disease. Int J Oral Sci 2010;2:198-207.
Sakai A, Ohshima M, Sugano N, Otsuka K, Ito K. Profiling the cytokines in gingival crevicular fluid using a cytokine antibody array. J Periodontol 2006;77:856-64.
Armitage GC. Development of a classification system for periodontal diseases and conditions. Ann Periodontol 1999;4:1-6.
Hosokawa Y, Hosokawa I, Ozaki K, Nakae H, Matsuo T. Oncostatin M synergistically induces CXCL10 and ICAM-1 expression in IL-1beta-stimulated-human gingival fibroblasts. J Cell Biochem 2010;111:40-8.
Kerfoot SM, Raharjo E, Ho M, Kaur J, Serirom S, McCafferty DM, et al
. Exclusive neutrophil recruitment with oncostatin M in a human system. Am J Pathol 2001;159:1531-9.
Huang FM, Tsai CH, Yang SF, Chang YC. The upregulation of oncostatin M in inflamed human dental pulps. Int Endod J 2009;42:627-31.
Manicourt DH, Poilvache P, Van Egeren A, Devogelaer JP, Lenz ME, Thonar EJ. Synovial fluid levels of tumor necrosis factor alpha and oncostatin M correlate with levels of markers of the degradation of crosslinked collagen and cartilage aggrecan in rheumatoid arthritis but not in osteoarthritis. Arthritis Rheum 2000;43:281-8.
Gwechenberger M, Moertl D, Pacher R, Huelsmann M. Oncostatin-M in myocardial ischemia/reperfusion injury may regulate tissue repair. Croat Med J 2004;45:149-57.
Badersten A, Nilvéus R, Egelberg J. Effect of nonsurgical periodontal therapy. I. Moderately advanced periodontitis. J Clin Periodontol 1981;8:57-72.
Genco RJ. Host responses in periodontal diseases: Current concepts. J Periodontol 1992;63 Suppl 4S:338-55.
George AK, Janam P. The short-term effects of non-surgical periodontal therapy on the circulating levels of interleukin-6 and C-reactive protein in patients with chronic periodontitis. J Indian Soc Periodontol 2013;17:36-41.
] [Full text]
Lin SJ, Chen YL, Kuo MY, Li CL, Lu HK. Measurement of gp130 cytokines oncostatin M and IL-6 in gingival crevicular fluid of patients with chronic periodontitis. Cytokine 2005;30:160-7.
Lu HK, Chen YL, Chang HC, Li CL, Kuo MY. Identification of the osteoprotegerin/receptor activator of nuclear factor-kappa B ligand system in gingival crevicular fluid and tissue of patients with chronic periodontitis. J Periodontal Res 2006;41:354-60.
Palmqvist P, Lundberg P, Lundgren I, Hänström L, Lerner UH. IL-1beta and TNF-alpha regulate IL-6-type cytokines in gingival fibroblasts. J Dent Res 2008;87:558-63.
Becerik S, Öztürk VÖ, Atmaca H, Atilla G, Emingil G. Gingival crevicular fluid and plasma acute-phase cytokine levels in different periodontal diseases. J Periodontol 2012;83:1304-13.
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]