Endoplasmic Reticulum Stress Regulates Rat Mandibular Cartilage Thinning under Compressive Mechanical Stress

Li, Huang; Zhang, Xiangyu; Wu, Tuojiang; Cheng, Wei; Liu, Xin; Jiang, Tingting; Wen, Juan; Li, Jie; Ma, Qiaoling; Hua, Zichun

doi:10.1074/jbc.m112.407296

Cited by 63 publications

(71 citation statements)

References 34 publications

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“…Osteoarthritis (OA) is a prevalent disorder characterized by accelerated chondrocyte terminal differentiation and extracellular matrix degradation in the cartilage of movable joints . OA is often caused by acute and chronic traumatic joint injuries .…”

Section: Introductionmentioning

confidence: 99%

Prevention of Injury-Induced Osteoarthritis in Rodent Temporomandibular Joint by Targeting Chondrocyte CaSR

Zhang

Yang

Wan

et al. 2018

Journal of Bone and Mineral Research

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Traumatic joint injuries produce osteoarthritic cartilage manifesting accelerated chondrocyte terminal differentiation and matrix degradation via unknown cellular and molecular mechanisms. Here we report the ability of biomechanical stress to increase expression of the calcium‐sensing receptor (CaSR), a pivotal driver of chondrocyte terminal differentiation, in cultured chondrogenic cells subjected to fluid flow shear stress (FFSS) and in chondrocytes of rodent temporomandibular joint (TMJ) cartilage subjected to unilateral anterior cross‐bite (UAC). In cultured ATDC5 cells or TMJ chondrocytes, FFSS induced Ca2+ loading and CaSR localization in endoplasmic reticulum (ER), casually accelerating cell differentiation that could be abrogated by emptying ER Ca2+ stores or CaSR knockdown. Likewise, acute chondrocyte‐specific Casr knockout (KO) prevented the UAC‐induced acceleration of chondrocyte terminal differentiation and matrix degradation in TMJ cartilage in mice. More importantly, local injections of CaSR antagonist, NPS2143, replicated the effects of Casr KO in preventing the development of osteoarthritic phenotypes in TMJ cartilage of the UAC‐treated rats. Our study revealed a novel pathological action of CaSR in development of osteoarthritic cartilage due to aberrant mechanical stimuli and supports a therapeutic potential of calcilytics in preventing osteoarthritis in temporomandibular joints by targeting the CaSR. © 2018 American Society for Bone and Mineral Research.

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Section: Introductionmentioning

confidence: 99%

Prevention of Injury-Induced Osteoarthritis in Rodent Temporomandibular Joint by Targeting Chondrocyte CaSR

Zhang

Yang

Wan

et al. 2018

Journal of Bone and Mineral Research

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“…It may also interact with other steroid receptors or thyroid receptors in a similar way 36. Furthermore, Calr was shown to be involved in cartilage thinning of mandibular cartilage in a rat model that studied the effects of compressive mechanical loading 37. In our forced running experiment, we see a similar induction of Calr expression upon stress, but not in the Dio2 knockout mice, possibly giving the knockout mouse an advantage against the formation of OA-like degradation or cartilage thinning.…”

Section: Discussionmentioning

confidence: 68%

The effect of forced exercise on knee joints in Dio2^−/− mice: type II iodothyronine deiodinase-deficient mice are less prone to develop OA-like cartilage damage upon excessive mechanical stress

et al. 2014

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Mice subjected to a running regime have significant increased cartilage damage and synovitis scores. Lack of Dio2 protected against cartilage damage in this model and was reflected in a specific gene expression profile, and either mark a favourable effect in the Dio2 knockout (eg, Gnas) or an unfavourable effect in wild-type cartilage homeostasis (eg, Hmbg2 and Calr). These data further support DIO2 activity as a therapeutic target in OA.

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“…Furthermore, our present study showed the effect of BIO was more significantly on the late loading stage (7 d). Our previous studies demonstrated that under compressive mechanical force stimulation, cartilage thinning was mostly mediated by apoptosis in the early stage at 4 d, and the inhibtion of apoptosis can partly rescue the cartilage thinning. However, the proliferation inhibition occurred more apparently in the late stage at 7 d. Therefore, it can be explained why the BIO treatment was more apparent in the late stage.…”

Section: Discussionmentioning

confidence: 97%

“…Each group was randomly divided into four subgroups with 12 animals in each subgroup, namely control (Con: Only injected with vehicle, that is, phosphate buffered saline, in one side of condyle), GSK3β inhibitor BIO alone (rats from Con subgroup injected with BIO in the opposite side of vehicle injection), Force (F: loaded with compressive mechanical force and injected with vehicle in one side of condyle), Force plus BIO (F + BIO: rats from F subgroup injected with BIO in the opposite side of vehicle injection). All of the rats in the F and F + BIO subgroup were loaded with compressive mechanical forces onto their TMJ as being previously described . In brief, the lower incisors of the rats were coated with the resin so that the two hooks made of 0.025‐inch stainless steel wire could not fall off.…”

Section: Methodsmentioning

confidence: 99%

“…Mandibular chondrocytes modulate the dynamic equilibrium between the degradation and synthesis of the extracellular matrix (ECM) in response to mechanical forces. When chondrocytes are decreased or functionally impaired by excessive mechanical force, pathological changes occur on cartilage and are usually followed by osteoarthritis (OA), which is well characterized by decreased chondrocyte proliferation, increased apoptosis, and degradation of the ECM . Therefore, how to rescue cartilage pathological changes became the major concern in the OA field.…”

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confidence: 99%

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BIO alleviated compressive mechanical force‐mediated mandibular cartilage pathological changes through Wnt/β‐catenin signaling activation

Jiang

Wen

Cheng

et al. 2017

Journal Orthopaedic Research

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Osteoarthritis induced by compressive mechanical force is characterized by decreased chondrocyte proliferation and degradation of the ECM. To examine underlying mechanisms of the pathological changes of mandibular cartilage induced by compressive mechanical force, an established animal model was used to examine Wnt signaling activation by glycogen synthase kinase-3 beta (GSK3β) inhibitor 6-Bromoindirubin-3'-oxime (BIO) injection in vivo. Histological changes in mandibular cartilage were assessed via hematoxylin & eosin (HE), masson, and alcian blue staining. Immunohistochemistry and real-time PCR were performed to evaluate activation of the Wnt signaling pathway and chondrocytes proliferation markers. Chondrocytes apoptosis was examined by TUNEL staining. During the compressive mechanical force loading-mediated process, Wnt signaling was largely inhibited, which showed the inhibited expression of β-catenin and the increased expression of GSK-3β. The expression of chondrocytes proliferation markers Ki67, and proliferating cell nuclear antigen (PCNA) also decreased. With BIO injection, the Wnt signaling was restored and the proliferation of mandibular chondrocytes was also increased in the late stage (7 days) of compressive mechanical force loading. Finally, the decreasing mandibular cartilage thickness, the degradation of extracellular matrix, and the erosion of bone trabecula were subsequently restored. Also, the changes of extracellular matrix markers such as collagen II and collagen X, matrix metalloproteases, and inflammatory cytokines were reversed followed by the injection of BIO. In summary, compressive mechanical force decreased endogenously Wnt signaling, leading to impaired proliferation in chondrocytes and degradation in cartilage matrix. Restoration of Wnt signaling largely recovered the proliferation defects and alleviated the pathological changes of mandibular cartilage. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1228-1237, 2018.

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Endoplasmic Reticulum Stress Regulates Rat Mandibular Cartilage Thinning under Compressive Mechanical Stress

Cited by 63 publications

References 34 publications

Prevention of Injury-Induced Osteoarthritis in Rodent Temporomandibular Joint by Targeting Chondrocyte CaSR

Prevention of Injury-Induced Osteoarthritis in Rodent Temporomandibular Joint by Targeting Chondrocyte CaSR

The effect of forced exercise on knee joints in Dio2^−/− mice: type II iodothyronine deiodinase-deficient mice are less prone to develop OA-like cartilage damage upon excessive mechanical stress

BIO alleviated compressive mechanical force‐mediated mandibular cartilage pathological changes through Wnt/β‐catenin signaling activation

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Endoplasmic Reticulum Stress Regulates Rat Mandibular Cartilage Thinning under Compressive Mechanical Stress

Cited by 63 publications

References 34 publications

Prevention of Injury-Induced Osteoarthritis in Rodent Temporomandibular Joint by Targeting Chondrocyte CaSR

Prevention of Injury-Induced Osteoarthritis in Rodent Temporomandibular Joint by Targeting Chondrocyte CaSR

The effect of forced exercise on knee joints in Dio2−/− mice: type II iodothyronine deiodinase-deficient mice are less prone to develop OA-like cartilage damage upon excessive mechanical stress

BIO alleviated compressive mechanical force‐mediated mandibular cartilage pathological changes through Wnt/β‐catenin signaling activation

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The effect of forced exercise on knee joints in Dio2^−/− mice: type II iodothyronine deiodinase-deficient mice are less prone to develop OA-like cartilage damage upon excessive mechanical stress