The role of TGF-ß1 in osteoarthritis of the temporomandibular joint in two genetic mouse models

Long, Evan; Motwani, Rohini; Reece, Daniel; Pettit, N.; Hepworth, Jared; Wong, Poo Sing; Reynolds, Paul; Seegmiller, Robert E.

doi:10.1016/j.archoralbio.2016.03.004

Cited by 21 publications

(20 citation statements)

References 17 publications

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“…We, for the first time, found that the expression of Tgf-β1 was increased in the condylar cartilage of an injurious model of OA. The increase in the expression of Tgf-β1 in the condylar cartilage in Col11a1 +/- mice was consistent with the observation from another independent report [17]. In the line with our present investigation, the protein expressions of Tgf-β1 and p-Smad2/3 were also elevated in the articular cartilage of a surgery mouse model of OA[11].…”

Section: Discussionsupporting

confidence: 93%

Conditional removal of the canonical TGF-β1 signaling delays condylar cartilage degeneration induced by a partial discectomy in mice

et al. 2017

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Recent emerging data indicate that the increase in the expression and activity of the transforming growth factor beta 1 (Tgf-β1) signaling may have detrimental effect to mature articular cartilage of knee joints. However, there is no information about whether or not this is the case in condylar cartilages. The objective of this study is to investigate the protein expression and activity of Tgf-β1 signaling in degenerative condylar cartilages. We also investigate biological effects of the conditional deletion of transforming growth factor receptor type II (Tgfbr2) in condylar cartilage of adult mice after a partial discectomy. Two mouse models of osteoarthritis (OA) were used to examine protein expressions of Tgf-β1 and p-Smad2/3 in condylar cartilages at early degenerative stages. In addition, cartilage specific Tgfbr2-deficient adult mice were subjected to a partial discectomy. The morphological condition of condylar cartilages was evaluated in mice at 4 and 12 weeks after the surgery. We found that protein levels of Tgf-β1 and p-Smad2/3 were increased in the degenerative condylar cartilage of the mouse models. The conditional removal of Tgfbr2 in mature condylar cartilage significantly delayed the progressive progression of the cartilage degeneration induced by a partial discectomy. We conclude that the increase in the expression and activity of Tgf-β1 signaling may have detrimental effect to mature condylar cartilages. Therefore, inhibition of Tgf-β1 signaling may be able to protect condylar cartilages from being degraded in mature temporomandibular joints.

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Section: Discussionsupporting

confidence: 93%

Conditional removal of the canonical TGF-β1 signaling delays condylar cartilage degeneration induced by a partial discectomy in mice

et al. 2017

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“…Although TGF-b1 expression is required for normal differentiation of cartilage in the early stages of joint development, after completion of chondrocyte differentiation in adult mice the increased expression of TGF-b1 appears unnecessary 12,13 . As the untreated cho/þ mutants exhibited significantly increased Mankin scores compared with the wild type, the overexpression of TGF-b1 observed in the TMJ of cho/þ mutants suggests involvement of this inflammatory molecule in the pathogenesis of TMJ OA 16 . Overexpression of TGF-b1 has also been observed in knee OA of cho/þ mutant mice at 3 months of age and in a surgical mouse model of knee OA 16,17 .…”

Section: Discussionmentioning

confidence: 93%

“…The scores of each genotype were averaged and compared for statistical significance; the higher the score implies more advanced OA histopathology. Both TMJ and knee joint tissues were also analyzed using the Osteoarthritis Research Society International (OARSI) procedure 16,28 . The statistical analysis in the present study is based on a two-way analysis of variance (ANOVA) , and was used to compare the means of each treatment group for statistically significant differences at the P < 0.05 level 26 .…”

Section: Tissue Evaluation and Histopathological Scoring Via Modifiedmentioning

confidence: 99%

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Losartan attenuates progression of osteoarthritis in the synovial temporomandibular and knee joints of a chondrodysplasia mouse model through inhibition of TGF-β1 signaling pathway

Thomas

Fronk

Gross

et al. 2019

Osteoarthritis and Cartilage

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High temperature requirement A1 serine protease (HtrA1) Losartan Osteoarthritis (OA) Temporomandibular joint (TMJ) Transforming growth factor-beta 1 (TGF-b1) s u m m a r y Objective: Transforming growth factor beta 1 (TGF-b1) is implicated in osteoarthritis (OA). The purpose of this study was to explore the ability of Losartan to inhibit the inflammatory signaling pathway of TGF-b1 observed during osteoarthritic progression in the temporomandibular joint (TMJ) and knee joint using a genetic mouse model. Methods: A murine OA model displaying the heterozygous chondrodysplasia gene (cho/þ), a col11a1 mutation, was used to test this hypothesis. Following a 7-month treatment period with Losartan, the synovial joints were analyzed for histopathological improvement comparing two experimental groups. Tissues were fixed in paraformaldehyde, processed to paraffin section, and stained with Safranin O and Fast Green to visualize proteoglycans and collagen proteins in cartilage. Using the Modified Mankin scoring system, the degree of staining and OA progression were evaluated. Results: Results show heterozygous animals receiving Losartan having diminished degeneration of TMJ condylar and knee joint articular cartilage. This was confirmed in the TMJ and knee by a statistically significant decrease in the Mankin histopathology score. Decreased expression of HtrA1, a key regulator to the TGF-b1 signaling pathway, was demonstrated in vitro as well as in vivo, via Losartan inhibition. Conclusion: Using a genetic mouse model of OA, this study demonstrated the utility of Losartan to improve treatment of human OA in the TMJ and knee joint through inhibition of the TGF-b1 signaling cascade. We further demonstrated inhibition of HtrA1, the lowering of Mankin scores to wild type control levels, and the limiting of OA progressive damage with treatment of Losartan.

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“…Genetic components are also discussed to be involved in the pathogenesis of TMJ osteoarthritis, i.e. : the expression of transforming growth factor-ß1 [15]. Furthermore, mRNA expression of the biomarkers: EGR1 (early growth response 1), EPHX1 (epoxide hydrolase 1), and IL10 (interleukin 10) coming from peripheral blood leukocytes are involved in the joint tissue damage and repair [16].…”

Section: Introductionmentioning

confidence: 99%

Morphology of the Temporomandibular Joints Regarding the Presence of Osteoarthritic Changes

Derwich

Mituś-Kenig

Pawłowska

2020

IJERPH

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1) Osteoarthritis, the most common disease of the temporomandibular joints (TMJs), is diagnosed by clinical and radiographic examination. Cone beam computed tomography (CBCT) is a method of choice for the imaging of osteoarthritic changes. The objective was to compare the morphology of the TMJs in CBCT images regarding the number of the osteoarthritic changes diagnosed in the area of the condyle. (2) A total of 105 patients participated in the study; their 210 TMJs were allocated into one of three groups regarding the number of diagnosed osteoarthritic changes: 1 (none or 1 type), 2 (2 types), 3 (3 or more types). The morphology of the TMJ was examined for each TMJ in the CBCT images. Statistical analysis was performed with STATISTICA version 12.0. The statistical significance level was p = 0.05 for all the measurements included. (3) The articular surface flattening was the most common type of the osteoarthritic changes (90%). The condylar A-P dimension differed significantly among the groups (p = 0.0001). The bigger the number of osteoarthritic changes diagnosed in one joint, the smaller the condylar A-P dimension that was observed. (4) The temporomandibular joints' osteoarthritic changes occur very often, even among asymptomatic patients. The increased number of osteoarthritic changes seems to have an impact on the condylar anteroposterior dimension. Author Contributions: Conceptualization, M.D.; methodology, M.D.; validation, M.D., M.M.-K., and E.P.; formal analysis, M.D.; investigation, M.D.; resources, M.D.; writing-original draft preparation, M.D.; writing-review and editing, M.M.-K. and E.P.; visualization, M.D.; supervision, M.M.-K. and E.P.; project administration, M.D., M.M.-K., and E.P. All authors have read and agreed to the published version of the manuscript. Funding: This research received no external funding. Conflicts of Interest:The authors declare no conflict of interest.

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The role of TGF-ß1 in osteoarthritis of the temporomandibular joint in two genetic mouse models

Cited by 21 publications

References 17 publications

Conditional removal of the canonical TGF-β1 signaling delays condylar cartilage degeneration induced by a partial discectomy in mice

Conditional removal of the canonical TGF-β1 signaling delays condylar cartilage degeneration induced by a partial discectomy in mice

Losartan attenuates progression of osteoarthritis in the synovial temporomandibular and knee joints of a chondrodysplasia mouse model through inhibition of TGF-β1 signaling pathway

Morphology of the Temporomandibular Joints Regarding the Presence of Osteoarthritic Changes

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