Molecular signaling in temporomandibular joint osteoarthritis

Lu, Ke; Ma, Feng; Yi, Dan; Yu, Huan; Tong, Liping; Chen, Di

doi:10.1016/j.jot.2021.07.001

Cited by 37 publications

(20 citation statements)

References 85 publications

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“…The progressive cartilage destruction and osteophyte formation are hallmarks of human TMJ OA; however, the underlying molecular mechanisms remain poorly defined. 7 Studies from different groups by using genetic mouse models showed that abnormalities in expression and activation in factors in Wnt/β-catenin, Runx2, FGF, MTORC1 signaling pathways are involved in initiation and progression in TMJ OA. For examples, Hui and co-workers reported that activation of β-catenin in Col2a1- or aggrecan-expressing chondrocytes causes multiple osteoarthritic defects in mouse TMJ, including aberrant chondrocyte hypertrophic differentiation, condylar cartilage degradation, rough articular surface and subchondral bone sclerosis.…”

Section: Discussionmentioning

confidence: 99%

“… 1 , 4 , 6 During the last decade, a range of genetically modified mouse models has been generated to investigate the regulatory mechanisms of TMJ OA. 7 Alterations in expression and/or activation of Wnt/β-catenin, fibroblast growth factors (FGFs), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and MTORC1 pathways, and abnormal and sustained mechanical loading have been linked to the pathogenesis of TMJ OA. 7 , 8 However, the molecular mechanisms underlying the initiation and progression of TMJ OA remain incompletely understood.…”

Section: Introductionmentioning

confidence: 99%

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Kindlin-2 loss in condylar chondrocytes causes spontaneous osteoarthritic lesions in the temporomandibular joint in mice

Lai

Zheng

et al. 2022

Int J Oral Sci

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The progressive destruction of condylar cartilage is a hallmark of the temporomandibular joint (TMJ) osteoarthritis (OA); however, its mechanism is incompletely understood. Here, we show that Kindlin-2, a key focal adhesion protein, is strongly detected in cells of mandibular condylar cartilage in mice. We find that genetic ablation of Kindlin-2 in aggrecan-expressing condylar chondrocytes induces multiple spontaneous osteoarthritic lesions, including progressive cartilage loss and deformation, surface fissures, and ectopic cartilage and bone formation in TMJ. Kindlin-2 loss significantly downregulates the expression of aggrecan, Col2a1 and Proteoglycan 4 (Prg4), all anabolic extracellular matrix proteins, and promotes catabolic metabolism in TMJ cartilage by inducing expression of Runx2 and Mmp13 in condylar chondrocytes. Kindlin-2 loss decreases TMJ chondrocyte proliferation in condylar cartilages. Furthermore, Kindlin-2 loss promotes the release of cytochrome c as well as caspase 3 activation, and accelerates chondrocyte apoptosis in vitro and TMJ. Collectively, these findings reveal a crucial role of Kindlin-2 in condylar chondrocytes to maintain TMJ homeostasis.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Kindlin-2 loss in condylar chondrocytes causes spontaneous osteoarthritic lesions in the temporomandibular joint in mice

Lai

Zheng

et al. 2022

Int J Oral Sci

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“…OA is a heterogeneous and complicated disease that affects multiple joints, such as the knee, hip, lumbar facet joint, and temporomandibular joint (TMJ). 10 , 11 The risk factors involved in knee and hip OA include genetics, aging, sex (female), race, occupation (physical labor), obesity, hypertension, abnormal joint strength lines, poor muscle strength, high-intensity exercise, and a history of joint injury. 12 – 18 These systemic susceptibility factors and local factors can cause abnormalities in signaling pathways and the related regulatory networks of key functional molecules that transmit pain signals and regulate chondrocyte homeostasis, survival and death and ultimately lead to joint pain and pathological cartilage changes in the synovial joint in OA.…”

Section: Introductionmentioning

confidence: 99%

Current understanding of osteoarthritis pathogenesis and relevant new approaches

Tong

Huang

et al. 2022

Bone Res

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Osteoarthritis (OA) is the most common degenerative joint disease that causes painful swelling and permanent damage to the joints in the body. The molecular mechanisms of OA are currently unknown. OA is a heterogeneous disease that affects the entire joint, and multiple tissues are altered during OA development. To better understand the pathological mechanisms of OA, new approaches, methods, and techniques need to be used to understand OA pathogenesis. In this review, we first focus on the epigenetic regulation of OA, with a particular focus on DNA methylation, histone modification, and microRNA regulation, followed by a summary of several key mediators in OA-associated pain. We then introduce several innovative techniques that have been and will continue to be used in the fields of OA and OA-associated pain, such as CRISPR, scRNA sequencing, and lineage tracing. Next, we discuss the timely updates concerning cell death regulation in OA pathology, including pyroptosis, ferroptosis, and autophagy, as well as their individual roles in OA and potential molecular targets in treating OA. Finally, our review highlights new directions on the role of the synovial lymphatic system in OA. An improved understanding of OA pathogenesis will aid in the development of more specific and effective therapeutic interventions for OA.

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“…In addition, in-depth understanding of the molecular mechanism underlying OA cartilage pathology will define novel targets for OA treatment. In this issue, Wnt/β-catenin, TGF-β and BMP, Indian Hedgehog, FGF, NF-κB, and Notch pathways have been summarized in the context of TMJ OA [ 3 ]. Alterations of these signaling pathways lead to the pathological changes in OA tissues, affecting cartilage matrix degradation, catabolic metabolism and chondrocyte apoptosis.…”

mentioning

confidence: 99%