Effects of mechanical stress and deficiency of dihydrotestosterone or 17β-estradiol on Temporomandibular Joint Osteoarthritis in mice

Ootake, Tomohisa; Ishii, Takenobu; Sueishi, Katsuo; Watanabe, Akira; Ishizuka, Yoichi; Amano, Katsuhiko; Nagao, Masashi; Nishimura, Kazuaki; Nishii, Yasushi

doi:10.1016/j.joca.2021.08.005

Cited by 10 publications

(8 citation statements)

References 40 publications

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Section: Discussionmentioning

confidence: 99%

“…Recently, several researchers have suggested that degenerative diseases of the TMJ, such as ICR and TMJ-OA, are caused by multiple etiological factors, including sex-hormone imbalances and excessive mechanical stress [ 20 , 21 ]. Ootake et al [ 21 ] investigated the interaction between excessive mechanical stress and decreased sex hormones on degenerative changes in the TMJ among orchiectomized (ORX) or ovariectomized (OVX) experimental mice, and demonstrated that excessive mechanical stress to the TMJ aggravates condylar deterioration in OVX and ORX mice. Wu et al [ 20 ] also reported that OVX mice with imbalanced occlusion (increased occlusal height) exhibited the most severe destruction of the condyle, suggesting that the combination of estrogen deficiency and excessive mechanical stress synergistically aggravates condylar resorption.…”

Section: Discussionmentioning

confidence: 99%

“…Wu et al [ 20 ] also reported that OVX mice with imbalanced occlusion (increased occlusal height) exhibited the most severe destruction of the condyle, suggesting that the combination of estrogen deficiency and excessive mechanical stress synergistically aggravates condylar resorption. In contrast, OVX and ORX mice without overloads to the TMJ did not exhibit condylar deterioration [ 20 , 21 ]. Although the pathophysiology of ICR remains unclear, intrinsic factors such as hormonal imbalances and immune disturbance might be contributory factors, and extrinsic factors such as mechanical overloading caused by orthodontic treatment, orthognathic surgery, imbalanced occlusion, and macrotrauma might accelerate condylar resorption.…”

Section: Discussionmentioning

confidence: 99%

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Signs, Symptoms, and Morphological Features of Idiopathic Condylar Resorption in Orthodontic Patients: A Survey-Based Study

Iwasa

Tanaka

2022

JCM

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Background: Idiopathic condylar resorption (ICR) is an aggressive degenerative disease of the temporomandibular joint that is most frequently observed in teenage girls. However, no specific cause of ICR has been identified. To explore the specific causes of the onset and progression of ICR, we performed a survey-based study on ICR in orthodontic patients and described its subjective symptoms, clinical signs, and condylar morphological features. Methods: A total of 1735 participants were recruited from 2193 orthodontic patients. For each participant, subjective symptoms and clinical signs of temporomandibular disorders (TMDs) were evaluated through clinical examination and a questionnaire. Furthermore, three-dimensional computed tomography (CT) was performed to diagnose ICR. Results: Among the 1735 patients evaluated, ICR was present in two male and ten female patients. All 12 patients had maxillary protrusion and an anterior open bite. Four patients with ICR underwent orthodontic treatment. Based on CT findings, patients with ICR had significantly different condylar sizes and shapes from patients with TMDs alone. Conclusions: The coexistence of intrinsic and extrinsic factors, such as sex-hormone imbalance and a history of orthodontic treatment, might lead to the onset of ICR. We suggest that growing patients suspected of having ICR should undergo CT evaluation because CT findings may precede clinical symptoms and signs.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Signs, Symptoms, and Morphological Features of Idiopathic Condylar Resorption in Orthodontic Patients: A Survey-Based Study

Iwasa

Tanaka

2022

JCM

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“… 48 The severity of TMJ-OA lesion was evaluated by the Mankin scoring system. 12 , 49 The TMJ-OA Mankin score was determined on sections stained with Safranin O-Fast Green. 50 …”

Section: Methodsmentioning

confidence: 99%

PTHrP promotes subchondral bone formation in TMJ-OA

Zhang

Zhou

et al. 2022

Int J Oral Sci

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PTH-related peptide (PTHrP) improves the bone marrow micro-environment to activate the bone-remodelling, but the coordinated regulation of PTHrP and transforming growth factor-β (TGFβ) signalling in TMJ-OA remains incompletely understood. We used disordered occlusion to establish model animals that recapitulate the ordinary clinical aetiology of TMJ-OA. Immunohistochemical and histological analyses revealed condylar fibrocartilage degeneration in model animals following disordered occlusion. TMJ-OA model animals administered intermittent PTHrP (iPTH) exhibited significantly decreased condylar cartilage degeneration. Micro-CT, histomorphometry, and Western Blot analyses disclosed that iPTH promoted subchondral bone formation in the TMJ-OA model animals. In addition, iPTH increased the number of osterix (OSX)-positive cells and osteocalcin (OCN)-positive cells in the subchondral bone marrow cavity. However, the number of osteoclasts was also increased by iPTH, indicating that subchondral bone volume increase was mainly due to the iPTH-mediated increase in the bone-formation ability of condylar subchondral bone. In vitro, PTHrP treatment increased condylar subchondral bone marrow-derived mesenchymal stem cell (SMSC) osteoblastic differentiation potential and upregulated the gene and protein expression of key regulators of osteogenesis. Furthermore, we found that PTHrP-PTH1R signalling inhibits TGFβ signalling during osteoblastic differentiation. Collectively, these data suggested that iPTH improves OA lesions by enhancing osteoblastic differentiation in subchondral bone and suppressing aberrant active TGFβ signalling. These findings indicated that PTHrP, which targets the TGFβ signalling pathway, may be an effective biological reagent to prevent and treat TMJ-OA in the clinic.

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“…Numerous studies have confirmed that it is a pathological state affected by multiple factors (Figure 1). Excessive mechanical stress is a major factor leading to cartilage rupture in TMJ (Su et al, 2014;Huang et al, 2021;Ootake et al, 2021). Uneven stress distribution in TMJ caused by occlusal disorder was reported to induce the hyperactivity of osteoclasts in subchondral bone.…”

Section: Introductionmentioning

confidence: 99%

A new frontier in temporomandibular joint osteoarthritis treatment: Exosome-based therapeutic strategy

Yuan

Huang

et al. 2022

Front. Bioeng. Biotechnol.

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Temporomandibular joint osteoarthritis (TMJOA) is a debilitating degenerative disease with high incidence, deteriorating quality of patient life. Currently, due to ambiguous etiology, the traditional clinical strategies of TMJOA emphasize on symptomatic treatments such as pain relief and inflammation alleviation, which are unable to halt or reverse the destruction of cartilage or subchondral bone. A number of studies have suggested the potential application prospect of mesenchymal stem cells (MSCs)-based therapy in TMJOA and other cartilage injury. Worthy of note, exosomes are increasingly being considered the principal efficacious agent of MSC secretions for TMJOA management. The extensive study of exosomes (derived from MSCs, synoviocytes, chondrocytes or adipose tissue et al.) on arthritis recently, has indicated exosomes and their specific miRNA components to be potential therapeutic agents for TMJOA. In this review, we aim to systematically summarize therapeutic properties and underlying mechanisms of MSCs and exosomes from different sources in TMJOA, also analyze and discuss the approaches to optimization, challenges, and prospects of exosome-based therapeutic strategy.

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Effects of mechanical stress and deficiency of dihydrotestosterone or 17β-estradiol on Temporomandibular Joint Osteoarthritis in mice

Cited by 10 publications

References 40 publications

Signs, Symptoms, and Morphological Features of Idiopathic Condylar Resorption in Orthodontic Patients: A Survey-Based Study

Signs, Symptoms, and Morphological Features of Idiopathic Condylar Resorption in Orthodontic Patients: A Survey-Based Study

PTHrP promotes subchondral bone formation in TMJ-OA

A new frontier in temporomandibular joint osteoarthritis treatment: Exosome-based therapeutic strategy

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