Kartogenin potentially protects temporomandibular joints from collagenase-induced osteoarthritis via core binding factor β and runt-related transcription factor 1 binding - A rat model study

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Abstract

Background/purpose

Temporomandibular joint (TMJ) osteoarthritis (TMJOA) is a chronic disease with progressive destruction of articular cartilage. This study aimed to explore the therapeutic effects of kartogenin on TMJOA via promoting the binding of core binding factor β (CBFβ) and runt-related transcription factor 1 (RUNX1).

Materials and methods

Type II collagenase was injected into 35 8-week-old male Sprague Dawley rat TMJs to establish the TMJOA model. Kartogenin, or the CBFβ-RUNX1 complex inhibitor (Ro5-3335), was also delivered via intra-articular injection. Subchondral bone was analyzed by MicroCT. The hematoxylin-eosin, Safranin O, and toluidine blue O staining were used to observe histopathology. Immunohistochemical staining of proliferating cell nuclear antigen (PCNA), caspase-3 (CASP3), interleukin-1β (IL-1β), and collagen II (COL2) was performed.

Results

TMJOA was established in rats by intra-articular injection of type II collagenase. The condylar cartilage and subchondral bone were damaged, with decreased PCNA and COL2 and increased CASP3 and IL-1 ( P < .001). Compared with the OA group, kartogenin alleviated the destruction of cartilage and subchondral bone, rescued the expression of PCNA and COL2, and decreased the expression of CASP3 and IL-1β ( P < .01). Ro5-3335 did not aggravate the pathology of TMJOA but neutralized the therapeutic effects of kartogenin on TMJOA.

Conclusion

Kartogenin has a potential therapeutic effect on TMJOA via promoting the CBFβ-RUNX1 binding.

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Most cited references 40

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Osteoarthritis cartilage histopathology: grading and staging.

K.P.H. Pritzker, S. Gay, S.A Jimenez … (2006)

Current osteoarthritis (OA) histopathology assessment methods have difficulties in their utility for early disease, as well as their reproducibility and validity. Our objective was to devise a more useful method to assess OA histopathology that would have wide application for clinical and experimental OA assessment and would become recognized as the standard method. An OARSI Working Group deliberated on principles, standards and features for an OA cartilage pathology assessment system. Using current knowledge of the pathophysiology of OA morphologic features, a proposed system was presented at OARSI 2000. Subsequently, this was widely circulated for comments amongst experts in OA pathology. An OA cartilage pathology assessment system based on six grades, which reflect depth of the lesion and four stages reflecting extent of OA over the joint surface was developed. The OARSI cartilage OA histopathology grading system appears consistent and simple to apply. Further studies are required to confirm the system's utility.

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Diagnostic Criteria for Temporomandibular Disorders (DC/TMD) for Clinical and Research Applications: recommendations of the International RDC/TMD Consortium Network* and Orofacial Pain Special Interest Group†.

Eric D Schiffman, Richard Ohrbach, Edmond L Truelove … (2014)

The original Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD) Axis I diagnostic algorithms have been demonstrated to be reliable. However, the Validation Project determined that the RDC/TMD Axis I validity was below the target sensitivity of ≥ 0.70 and specificity of ≥ 0.95. Consequently, these empirical results supported the development of revised RDC/TMD Axis I diagnostic algorithms that were subsequently demonstrated to be valid for the most common pain-related TMD and for one temporomandibular joint (TMJ) intra-articular disorder. The original RDC/TMD Axis II instruments were shown to be both reliable and valid. Working from these findings and revisions, two international consensus workshops were convened, from which recommendations were obtained for the finalization of new Axis I diagnostic algorithms and new Axis II instruments. Through a series of workshops and symposia, a panel of clinical and basic science pain experts modified the revised RDC/TMD Axis I algorithms by using comprehensive searches of published TMD diagnostic literature followed by review and consensus via a formal structured process. The panel's recommendations for further revision of the Axis I diagnostic algorithms were assessed for validity by using the Validation Project's data set, and for reliability by using newly collected data from the ongoing TMJ Impact Project-the follow-up study to the Validation Project. New Axis II instruments were identified through a comprehensive search of the literature providing valid instruments that, relative to the RDC/TMD, are shorter in length, are available in the public domain, and currently are being used in medical settings. The newly recommended Diagnostic Criteria for TMD (DC/TMD) Axis I protocol includes both a valid screener for detecting any pain-related TMD as well as valid diagnostic criteria for differentiating the most common pain-related TMD (sensitivity ≥ 0.86, specificity ≥ 0.98) and for one intra-articular disorder (sensitivity of 0.80 and specificity of 0.97). Diagnostic criteria for other common intra-articular disorders lack adequate validity for clinical diagnoses but can be used for screening purposes. Inter-examiner reliability for the clinical assessment associated with the validated DC/TMD criteria for pain-related TMD is excellent (kappa ≥ 0.85). Finally, a comprehensive classification system that includes both the common and less common TMD is also presented. The Axis II protocol retains selected original RDC/TMD screening instruments augmented with new instruments to assess jaw function as well as behavioral and additional psychosocial factors. The Axis II protocol is divided into screening and comprehensive self report instrument sets. The screening instruments' 41 questions assess pain intensity, pain-related disability, psychological distress, jaw functional limitations, and parafunctional behaviors, and a pain drawing is used to assess locations of pain. The comprehensive instruments, composed of 81 questions, assess in further detail jaw functional limitations and psychological distress as well as additional constructs of anxiety and presence of comorbid pain conditions. The recommended evidence-based new DC/TMD protocol is appropriate for use in both clinical and research settings. More comprehensive instruments augment short and simple screening instruments for Axis I and Axis II. These validated instruments allow for identification of patients with a range of simple to complex TMD presentations.

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A stem cell-based approach to cartilage repair.

Kristen Johnson, Shoutian Zhu, Matthew S Tremblay … (2012)

Osteoarthritis (OA) is a degenerative joint disease that involves the destruction of articular cartilage and eventually leads to disability. Molecules that promote the selective differentiation of multipotent mesenchymal stem cells (MSCs) into chondrocytes may stimulate the repair of damaged cartilage. Using an image-based high-throughput screen, we identified the small molecule kartogenin, which promotes chondrocyte differentiation (median effective concentration = 100 nM), shows chondroprotective effects in vitro, and is efficacious in two OA animal models. Kartogenin binds filamin A, disrupts its interaction with the transcription factor core-binding factor β subunit (CBFβ), and induces chondrogenesis by regulating the CBFβ-RUNX1 transcriptional program. This work provides new insights into the control of chondrogenesis that may ultimately lead to a stem cell-based therapy for osteoarthritis.

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Author and article information

Contributors

Yubin Cao

Jian Pan

Journal

Journal ID (nlm-ta): J Dent Sci

Journal ID (iso-abbrev): J Dent Sci

Title: Journal of Dental Sciences

Publisher: Association for Dental Sciences of the Republic of China

ISSN (Print): 1991-7902

ISSN (Electronic): 2213-8862

Publication date PMC-release: 14 March 2023

Publication date (Print): October 2023

Publication date (Electronic): 14 March 2023

Volume: 18

Issue: 4

Pages: 1553-1560

Affiliations

[a ]State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China

[b ]Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, China

Author notes

[∗ ]Corresponding author. West China Hospital of Stomatology, Sichuan University, No.14, Section 3rd, Renmin Nan Road, Chengdu, 610041, China. yubin.cao@ 123456scu.edu.cn

[∗∗ ]Corresponding author. West China Hospital of Stomatology, Sichuan University, No.14, Section 3rd, Renmin Nan Road, Chengdu, 610041, China. jianpancn@ 123456scu.edu.cn

[1]

These authors contributed equally to this work.

Article

Publisher Item ID: S1991-7902(23)00062-4

DOI: 10.1016/j.jds.2023.03.002

PMC ID: 10548007

PubMed ID: 37799879

SO-VID: ff21c7dd-25fe-45ae-9e0b-7d2446453f83

License:

This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Kartogenin potentially protects temporomandibular joints from collagenase-induced osteoarthritis via core binding factor β and runt-related transcription factor 1 binding - A rat model study

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Abstract

Background/purpose

Materials and methods

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Conclusion

Related collections

ChemSpider related publications

Most cited references 40

Osteoarthritis cartilage histopathology: grading and staging.

Diagnostic Criteria for Temporomandibular Disorders (DC/TMD) for Clinical and Research Applications: recommendations of the International RDC/TMD Consortium Network* and Orofacial Pain Special Interest Group†.

A stem cell-based approach to cartilage repair.

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