The Role of Parathyroid Hormone‐Related Protein in the Regulation of Osteoclastogenesis by Cementoblasts

Boabaid, Fernanda; Berry, Janice E.; Koh, Amy J.; Somerman, Martha J.; McCauley, Laurie K.

doi:10.1902/jop.2004.75.9.1247

Cited by 85 publications

(53 citation statements)

References 38 publications

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“…While cementoblasts express RANKL and OPG [36], it has remained unreported whether cementocytes express RANKL or OPG, and if the cells play a parallel role to osteocytes in controlling osteoclast activation around the tooth root.…”

Section: Resultsmentioning

confidence: 99%

Isolation and Functional Analysis of an Immortalized Murine Cementocyte Cell Line, IDG-CM6

Zhao

Nociti

Duan

et al. 2015

Journal of Bone and Mineral Research

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The dental cementum covering the tooth root is similar to bone in several respects, but remains poorly understood in terms of development and differentiation of cementoblasts, as well as the potential function(s) of cementocytes residing in the cellular cementum. It is not known if the cementocyte is a dynamic actor in cementum metabolism, comparable to the osteocyte in the bone. Cementocytes exhibit irregular spacing and lacunar shape, with fewer canalicular connections compared to osteocytes. Immunohistochemistry and quantitative PCR (qPCR) revealed that the in vivo expression profile of cementocytes paralleled that of osteocytes, including expression of dentin matrix protein 1 (Dmp1/DMP1), Sost/sclerostin, E11/gp38/podoplanin, Tnfrsf11b (osteoprotegerin; OPG), and Tnfsf11 (receptor activator of NF-kB ligand; RANKL). We used the Immortomouse+/−; Dmp1-GFP+/− mice to isolate cementocytes as Dmp1-expressing cells followed by immortalization using the interferon (IFN)-γ-inducible promoter driving expression of a thermolabile large T antigen to create the first immortalized line of cementocytes, IDG-CM6. This cell line reproduced the expression profile of cementocytes observed in vivo, including alkaline phosphatase activity and mineralization. IDG-CM6 cells expressed higher levels of Tnfrsf11b, and lower levels of Tnfsf11 compared to IDG-SW3 osteocytes, and under fluid flow shear stress, IDG-CM6 cells significantly increased OPG while decreasing RANKL, leading to a significantly increased OPG/RANKL ratio, which would inhibit osteoclast activation. These studies indicate similarities yet potentially important differences in the function of cementocytes as compared to osteocytes and support cementocytes as mechanically responsive cells.

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Section: Resultsmentioning

confidence: 99%

Isolation and Functional Analysis of an Immortalized Murine Cementocyte Cell Line, IDG-CM6

Zhao

Nociti

Duan

et al. 2015

Journal of Bone and Mineral Research

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“…Histopathological scores of joint damage were determined for inflammatory infiltrate, synovitis, cartilage destruction, and bone involvement as described elsewhere [30]. For TRAP staining, slides were deparaffinized in xylene, hydrated in serial ethanol, and incubated in a solution containing diazotized fast garnet, napthol AS-BI phosphate, acetate, and tartrate solution from the Acid Phosphatase, Leukocyte (TRAP) kit (Sigma-Aldrich) as described previously [35]. Osteoclasts were identified as TRAP-positive cells and counted utilizing Osteomeasure software (Osteometrics, Inc., Decatur, GA, USA).…”

Section: Methodsmentioning

confidence: 99%

Porphyromonas gingivalis oral infection exacerbates the development and severity of collagen-induced arthritis

et al. 2013

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IntroductionClinical studies suggest a direct influence of periodontal disease (PD) on serum inflammatory markers and disease assessment of patients with established rheumatoid arthritis (RA). However, the influence of PD on arthritis development remains unclear. This investigation was undertaken to determine the contribution of chronic PD to immune activation and development of joint inflammation using the collagen-induced arthritis (CIA) model.MethodsDBA1/J mice orally infected with Porphyromonas gingivalis were administered with collagen II (CII) emulsified in complete Freund’s adjuvant (CFA) or incomplete Freund’s adjuvant (IFA) to induce arthritis. Arthritis development was assessed by visual scoring of paw swelling, caliper measurement of the paws, mRNA expression, paw micro-computed tomography (micro-CT) analysis, histology, and tartrate resistant acid phosphatase for osteoclast detection (TRAP)-positive immunohistochemistry. Serum and reactivated splenocytes were evaluated for cytokine expression.ResultsMice induced for PD and/or arthritis developed periodontal disease, shown by decreased alveolar bone and alteration of mRNA expression in gingival tissues and submandibular lymph nodes compared to vehicle. P. gingivalis oral infection increased paw swelling and osteoclast numbers in mice immunized with CFA/CII. Arthritis incidence and severity were increased by P. gingivalis in mice that received IFA/CII immunizations. Increased synovitis, bone erosions, and osteoclast numbers in the paws were observed following IFA/CII immunizations in mice infected with P gingivalis. Furthermore, cytokine analysis showed a trend toward increased serum Th17/Th1 ratios when P. gingivalis infection was present in mice receiving either CFA/CII or IFA/CII immunizations. Significant cytokine increases induced by P. gingivalis oral infection were mostly associated to Th17-related cytokines of reactivated splenic cells, including IL-1β, IL-6, and IL-22 in the CFA/CII group and IL-1β, tumor necrosis factor-α, transforming growth factor-β, IL-6 and IL-23 in the IFA/CII group.ConclusionsChronic P. gingivalis oral infection prior to arthritis induction increases the immune system activation favoring Th17 cell responses, and ultimately accelerating arthritis development. These results suggest that chronic oral infection may influence RA development mainly through activation of Th17-related pathways.

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“…This process required osteoclasts and cementoblasts. Cementoblasts participated in the root repair process and in the regulation of the differentiation and absorption functions of osteoclasts, and they also affected root absorption (Boabaid et al, 2004;Marchesan et al, 2013;Yang et al, 2015). In recent years, the OPG and RANKL system was found to be an important signal pathway in the differentiation of osteoclasts, which was widely involved in bone cell growth.…”

Section: Discussionmentioning

confidence: 99%

Expression of OPG, RANKL, and RUNX2 in rabbit periodontium under orthodontic force

Zhang

Wang³

et al. 2015

Genet. Mol. Res.

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ABSTRACT. This study aims to investigate the expression changes of RANKL, RUNX2, and OPG in rabbit periodontal tissues under orthodontic force and explore its effect on the remodeling of periodontal tissues. A total of 16 specific pathogen-free rabbits were used in this study. The maxillary appliance was worn on the right (experimental) side, and the appliance-free left side was used as the control. Rabbits were sacrificed after 3, 5, 7, and 14 days of treatment. Changes in the expression levels of OPG, RANKL, and RUNX2 in the periodontium were detected using real-time PCR and western blotting methods. The OPG expression levels decreased after 3 to 14 days of treatment, while the expression levels of RANKL and RUNX2 increased after 3 to 14 days. The OPG expression levels decreased while those of RANKL and RUNX2 increased during orthodontic tooth movement, 19383OPG, RANKL, RUNX2 and fault micromaxillary deformity ©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 14 (4): 19382-19388 (2015) which suggested that they play a role in the osteogenesis process and the reconstruction of periodontal tissue.

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The Role of Parathyroid Hormone‐Related Protein in the Regulation of Osteoclastogenesis by Cementoblasts

Abstract: These results demonstrate that PTHrP influences the balance of OPG and RANKL production by cementoblasts, and further indicate that this effect, in the context of surrounding cells, might have a significant impact on osteoclastogenesis, root resorption, and tooth eruption.

Cited by 85 publications

References 38 publications

Isolation and Functional Analysis of an Immortalized Murine Cementocyte Cell Line, IDG-CM6

Isolation and Functional Analysis of an Immortalized Murine Cementocyte Cell Line, IDG-CM6

Porphyromonas gingivalis oral infection exacerbates the development and severity of collagen-induced arthritis

Expression of OPG, RANKL, and RUNX2 in rabbit periodontium under orthodontic force

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