The Novel Antioxidant Compound JSH-23 Prevents Osteolysis by Scavenging ROS During Both Osteoclastogenesis and Osteoblastogenesis

Mei, Liangwei; Zheng, Yi; Ma, Teng; Xia, Bing; Gao, Xue; Hao, Yiming; Luo, Zhuojing; Huang, Jinghui

doi:10.3389/fphar.2021.734774

Cited by 6 publications

(6 citation statements)

References 59 publications

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“…Interestingly, pharmacological downregulation of ROS leads to reduced numbers of mature osteoclasts as well as decreased resorbing activity in the remaining OC via RANKL/NFATc1 signaling without cytotoxicity ( 29 , 50 , 51 ). As the intracellular ROS level is reduced by exposure to low doses of X-rays ( 52 ), this reduced level of oxidative stress could be one cause for the reduced resorbing activity of irradiated OC precursors in our study.…”

Section: Discussionmentioning

confidence: 99%

Modulation of Differentiation and Bone Resorbing Activity of Human (Pre-) Osteoclasts After X-Ray Exposure

et al. 2022

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Low-dose radiotherapy (LD-RT) is a local treatment option for patients with chronic degenerative and inflammatory diseases, in particular musculoskeletal diseases. Despite reported analgesic and anti-inflammatory effects, cellular and molecular mechanisms related to osteoimmunological effects are still elusive. Here we test the hypothesis that X-irradiation inhibits the differentiation of precursor osteoclasts into mature osteoclasts (mOC) and their bone resorbing activity. Circulating monocytes from healthy donors were isolated and irradiated after attachment with single or fractionated X-ray doses, comparable to an LD-RT treatment scheme. Then monocytes underwent ex vivo differentiation into OC during cultivation up to 21 days, under conditions mimicking the physiological microenvironment of OC on bone. After irradiation, apoptotic frequencies were low, but the total number of OC precursors and mOC decreased up to the end of the cultivation period. On top, we observed an impairment of terminal differentiation, i.e. a smaller fraction of mOC, reduced resorbing activity on bone, and release of collagen fragments. We further analyzed the effect of X-irradiation on multinucleation, resulting from the fusion of precursor OC, which occurs late during OC differentiation. At 21 days after exposure, the observation of smaller cellular areas and a reduced number of nuclei per mOC suggest an impaired fusion of OC precursors to form mOC. Before, at 14 days, the nuclear translocation of Nuclear Factor Of Activated T Cells 1 (NFATc1), a master regulator of osteoclast differentiation and fusion, was decreased. In first results, obtained in the frame of a longitudinal LD-RT study, we previously reported a pain-relieving effect in patients. However, in a subgroup of patients suffering from Calcaneodynia or Achillodynia, we did not observe a consistent decrease of established blood markers for resorption and formation of bone, or modified T cell subtypes involved in regulating these processes. To assess the relevance of changes in bone metabolism for other diseases treated with LD-RT will be subject of further studies. Taken together, we observed that in vitro X-irradiation of monocytes results in an inhibition of the differentiation into bone-resorbing OC and a concomitant reduction of resorbing activity. The detected reduced NFATc1 signaling could be one underlying mechanism.

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Section: Discussionmentioning

confidence: 99%

Modulation of Differentiation and Bone Resorbing Activity of Human (Pre-) Osteoclasts After X-Ray Exposure

et al. 2022

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“…The ROS level in the distal femurs was assessed by DHE fluorescence, as previously described . In a nutshell, the samples received 4 weeks of fixation in 4% PFA, then were subjected to a gentle decalcification in solutions containing 10% EDTA.…”

Section: Methodsmentioning

confidence: 99%

“…The ROS level in the distal femurs was assessed by DHE fluorescence, as previously described. 7 In a nutshell, the samples received 4 weeks of fixation in 4% PFA, then were subjected to a gentle decalcification in solutions containing 10% EDTA. After that, the decalcified bones were submerged for 3 days in a solution consisting of 20% sucrose and 2% poly(vinylpyrrolidone).…”

Section: Ros Level In the Distalmentioning

confidence: 99%

“…Though reactive oxygen species (ROS) can stimulate OCG and osteoclastic differentiation, excessive production of ROS is harmful to osteoblastogenesis and bone homeostasis. , Stimulation by RANKL, a molecule that activates osteoclast precursors, leads to the generation of endogenous ROS like NADPH oxidase 1 (Nox1) and Ras-related C3 botulinum toxin substrate 1 (Rac1) via RANK . Additionally, suppressing ROS production can prevent OCG. , The Nrf2 transcription factor belongs to the NFE2 family, which regulates the production of antioxidant enzymes, like heme oxygenase-1 (HO-1), NAD(P)H: quinone oxidoreductase 1 (NQO1), and Catalase.…”

Section: Introductionmentioning

confidence: 99%

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Corynoline Suppresses Osteoclastogenesis and Attenuates ROS Activities by Regulating NF-κB/MAPKs and Nrf2 Signaling Pathways

Jin,

Yu,

Yang

et al. 2024

J. Agric. Food Chem.

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Declining estrogen production in postmenopausal females causes osteoporosis in which the resorption of bone exceeds the increase in bone formation. Although clinical drugs are currently available for the treatment of osteoporosis, sustained medication use is accompanied by serious side effects. Corydalis bungeana Herba, a famous traditional Chinese herb listed in the Chinese Pharmacopoeia Commission, constitutes various traditional Chinese Medicine prescriptions, which date back to thousands of years. One of the primary active components of C. bungeana Turcz. is Corynoline (Cor), a plant isoquinoline alkaloid derived from the Corydalis species, which possesses bone metabolism disease therapeutic potential. The study aimed at exploring the effects as well as mechanisms of Cor on osteoclast formation and bone resorption. TRAcP staining, F-actin belt formation, and pit formation were employed for assessing the osteoclast function. Western blot, qPCR, network pharmacology, and docking analyses were used for analyzing the expression of osteoclast-associated genes and related signaling pathways. The study focused on investigating how Cor affected OVX-induced trabecular bone loss by using a mouse model. Cor could weaken osteoclast formation and function by affecting the biological receptor activators of NF-κB and its ligand at various concentrations. Mechanistically, Cor inhibited the NF-κB activation, and the MAPKs pathway stimulated by RANKL. Besides, Cor enhanced the protein stability of the Nrf2, which effectively abolished the RANKL-stimulated ROS generation. According to an OVX mouse model, Cor functions in restoring bone mass, improving microarchitecture, and reducing the ROS levels in the distal femurs, which corroborated with its in vitro antiosteoclastogenic effect. The present study indicates that Cor may restrain osteoclast formation and bone loss by modulating NF-κB/MAPKs and Nrf2 signaling pathways. Cor was shown to be a potential drug candidate that can be utilized for the treatment of osteoporosis.

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“…9 HO-1 induction through transient gene vectors or bioactive small molecules impedes osteoclastogenesis. 10 In contrast, previous research has demonstrated that the suppression of HO-1 using RNA interference facilitates the development of osteoclasts. 11 The results of this study indicate that the activation of HO-1 expression by some drugs may confer a protective effect against pathological conditions characterized by the deterioration of bone tissue.…”

mentioning

confidence: 92%

Potato protein hydrolysate inhibits RANKL‐induced osteoclast development by inhibiting osteoclastogenic genes via the NF‐κB/MAPKs signaling pathways

Chen,

He,

et al. 2024

Environmental Toxicology

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In recent times, there has been growing attention towards exploring the nutritional and functional aspects of potato protein, along with its diverse applications. In the present study, we examined the anti‐osteoclast properties of potato protein hydrolysate (PP902) in vitro. Murine macrophages (RAW264.7) were differentiated into osteoclasts by receptor activator of nuclear factor‐κB ligand (RANKL), and PP902 was examined for its inhibitory effect. Initially, treatment with PP902 was found to significantly prevent RANKL‐induced morphological changes in macrophage cells, as determined by tartrate‐resistant acid phosphatase (TRAP) staining analysis. This notion was further supported by F‐actin analysis using a confocal microscope. Furthermore, PP902 treatment effectively and dose‐dependently down‐regulated the expression of RANKL‐induced osteoclastogenic marker genes, including TRAP, CTR, RANK, NFATc1, OC‐STAMP, and c‐Fos. These inhibitory effects were associated with suppressing NF‐κB transcriptional activation and subsequent reduced nuclear translocation. The decrease in NF‐κB activity resulted from reduced activation of its upstream kinases, including I‐κBα and IKKα. Moreover, PP902 significantly inhibited RANKL‐induced p38MAPK and ERK1/2 activities. Nevertheless, PP902 treatment prevents RANKL‐induced intracellular reactive oxygen species generation via increased HO‐1 activity. The combined antioxidant and anti‐inflammatory effects of PP902 resulted in significant suppression of osteoclastogenesis, suggesting its potential as an adjuvant therapy for osteoclast‐related diseases.

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The Novel Antioxidant Compound JSH-23 Prevents Osteolysis by Scavenging ROS During Both Osteoclastogenesis and Osteoblastogenesis

Cited by 6 publications

References 59 publications

Modulation of Differentiation and Bone Resorbing Activity of Human (Pre-) Osteoclasts After X-Ray Exposure

Modulation of Differentiation and Bone Resorbing Activity of Human (Pre-) Osteoclasts After X-Ray Exposure

Corynoline Suppresses Osteoclastogenesis and Attenuates ROS Activities by Regulating NF-κB/MAPKs and Nrf2 Signaling Pathways

Potato protein hydrolysate inhibits RANKL‐induced osteoclast development by inhibiting osteoclastogenic genes via the NF‐κB/MAPKs signaling pathways

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