Deletion of <i>Runx2</i> in condylar chondrocytes disrupts TMJ tissue homeostasis

Liao, Lin; Zhang, Shanxing; Zhou, Guangqian; Ye, Ling; Zhao, Lan; Chen, Di

doi:10.1002/jcp.26761

Cited by 25 publications

(19 citation statements)

References 29 publications

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“…Our previous studies demonstrated that Agc1-CreER T2 mice could efficiently drive Cre expression in TMJ cells. 26 , 49 Cre-negative littermates were used as the control group. β-catenin Act mice and Cre-negative littermates (male) were administered tamoxifen (Sigma, St. Louis, MO, USA) by i.p.…”

Section: Methodsmentioning

confidence: 99%

Nociceptive behavioural assessments in mouse models of temporomandibular joint disorders

et al. 2020

Int J Oral Sci

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Orofacial pain or tenderness is a primary symptom associated with temporomandibular joint (TMJ) disorders (TMDs). To understand the pathological mechanisms underlying TMDs, several mouse models have been developed, including mechanical stimulus-induced TMD and genetic mouse models. However, a lack of feasible approaches for assessing TMD-related nociceptive behaviours in the orofacial region of mice has hindered the in-depth study of TMD-associated mechanisms. This study aimed to explore modifications of three existing methods to analyse nociceptive behaviours using two TMD mouse models: (1) mechanical allodynia was tested using von Frey filaments in the mouse TMJ region by placing mice in specially designed chambers; (2) bite force was measured using the Economical Load and Force (ELF) system; and (3) spontaneous feeding behaviour tests, including eating duration and frequency, were analysed using the Laboratory Animal Behaviour Observation Registration and Analysis System (LABORAS). We successfully assessed changes in nociceptive behaviours in two TMD mouse models, a unilateral anterior crossbite (UAC)-induced TMD mouse model and a β-catenin conditional activation mouse model. We found that the UAC model and β-catenin conditional activation mouse model were significantly associated with signs of increased mechanical allodynia, lower bite force, and decreased spontaneous feeding behaviour, indicating manifestations of TMD. These behavioural changes were consistent with the cartilage degradation phenotype observed in these mouse models. Our studies have shown reliable methods to analyse nociceptive behaviours in mice and may indicate that these methods are valid to assess signs of TMD in mice.

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Section: Methodsmentioning

confidence: 99%

Nociceptive behavioural assessments in mouse models of temporomandibular joint disorders

et al. 2020

Int J Oral Sci

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“…Multiple transcription factors (TFs) and signaling pathways regulate hypertrophic chondrocyte-specific Col10a1 expression in vitro and in vivo (Lu et al, 2014). Of these, Runx2 is essential for osteoblast differentiation and chondrocyte hypertrophy (Komori et al, 1997;Lee et al, 1997;Otto et al, 1997;Komori, 2018;Liao et al, 2019;Qin et al, 2020) and is a major transcriptional determinant for Col10a1 expression across species (Drissi et al, 2003;Simoes et al, 2006;Higashikawa et al, 2009). In our work on mouse Col10a1 regulation, we found that Runx2 directly interacts with the Col10a1 proximal promoter and 150-bp enhancer and is an indispensable Col10a1 regulator (Zheng et al, 2003(Zheng et al, , 2009Li et al, 2011).…”

Section: Introductionmentioning

confidence: 92%

Expression Profiling and Functional Analysis of Candidate Col10a1 Regulators Identified by the TRAP Program

et al. 2021

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Hypertrophic chondrocytes and their specific marker, the type X collagen gene (Col10a1), are critical components of endochondral bone formation during skeletal development. We previously found that Runx2 is an indispensable mouse Col10a1 gene regulator and identified many other transcription factors (TFs) that potentially interact with the 150-bp Col10a1 cis-enhancer. However, the roles of these candidate TFs in Col10a1 expression and chondrocyte hypertrophy have not been elucidated. Here, we focus on 32 candidate TFs recently identified by analyzing the 150-bp Col10a1 enhancer using the transcription factor affinity prediction (TRAP) program. We found that 12 TFs (Hoxa3, Lsx, Evx2, Dlx5, S8, Pax2, Egr2, Mef2a, Barhl2, GKlf, Sox17, and Crx) were significantly upregulated and four TFs (Lhx4, Tbx5, Mef2c, and Hb9) were significantly downregulated in hypertrophic MCT cells, which show upregulation of Col10a1 expression. Most of the differential expression pattern of these TFs conformed with the results obtained from ATDC5 cell model and primary mouse chondrocytes. Notably, Tbx5 was downregulated upon Col10a1 upregulation, overexpression of Tbx5 decreased Col10a1 expression, and knock-down of Tbx5 increased Col10a1 expression in hypertrophic chondrocytes, suggesting that Tbx5 is a negative regulator of Col10a1. We further generated a stable Tbx5-overexpressing ATDC5 cell line and ColX-Tbx5 transgenic mice driven by Col10a1-specific enhancers and promoters. Tbx5 overexpression decreased Col10a1 expression in ATDC5 cells cultured as early as day 7 and in limb tissue on post-natal day 1. Slightly weaker alkaline phosphatase staining was also observed in cell culture on day 7 and in limb digits on embryonic day 17.5, indicating mildly delayed ossification. Further characterization of these candidate Col10a1 transcriptional regulators could help identify novel therapeutic targets for skeletal diseases associated with abnormal chondrocyte hypertrophy.

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“…Interestingly, Runx2 deletion blocks chondrocyte translocation into the subchondral bone region and inhibits chondrocyte transdifferentiation into progenitor cells [ 89 ]. Comparatively, histological analysis demonstrated extensive chondrocyte growth in condylar cartilage and subchondral bone in control mice, indicating a key role for Runx2 in subchondral bone remodeling [ 89 ]. Runx2 was also highly expressed in proliferative and hypertrophic chondrocytes, suggesting Runx2 regulates subchondral bone remodeling.…”

Section: Runx2 Functions In Different Joint Tissuesmentioning

confidence: 99%

Runx2 plays a central role in Osteoarthritis development

Chen

Kim

Shen

et al. 2020

Journal of Orthopaedic Translation

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Osteoarthritis (OA) is the most common form of arthritis, is the leading cause of impaired mobility in the elderly, and accounts for more than a third of chronic moderate to severe pain. As a degenerative joint disorder, OA affects the whole joint and results in synovial hyperplasia, degradation of articular cartilage, subchondral sclerosis, osteophyte formation, and chronic pain. Currently, there is no effective drug to decelerate OA progression and molecular targets for drug development have been insufficiently investigated. Anti-OA drug development can benefit from more and precise knowledge of molecular targets for drug development. Runt-related transcription factor 2 (Runx2) is a key transcription factor controlling osteoblast and chondrocyte differentiation and is among the most promising potential therapeutic targets. Notably, Runx2 expression is upregulated in several murine OA models, suggesting a role in disease pathogenesis. In this review article, we summarized recent findings on Runx2 related to OA development and evaluated its potential as a therapeutic target. The translational potential of this article A better understanding of the role of Runx2 in osteoarthritis pathogenesis will contribute to the development of novel intervention of osteoarthritis disease.

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Deletion of Runx2 in condylar chondrocytes disrupts TMJ tissue homeostasis

Cited by 25 publications

References 29 publications

Nociceptive behavioural assessments in mouse models of temporomandibular joint disorders

Nociceptive behavioural assessments in mouse models of temporomandibular joint disorders

Expression Profiling and Functional Analysis of Candidate Col10a1 Regulators Identified by the TRAP Program

Runx2 plays a central role in Osteoarthritis development

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