Obatoclax Regulates the Proliferation and Fusion of Osteoclast Precursors through the Inhibition of ERK Activation by RANKL

Oh, Ju‐Hee; Lee, Jae Yoon; Park, Jin Hyeong; No, Jeong Hyeon; Lee, Na Kyung

doi:10.14348/molcells.2015.2340

Cited by 16 publications

(13 citation statements)

References 38 publications

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“…Although the dramatic decrease of osteoclast fusion in the presence of ERK1 siRNA could be recovered by the collagenase inhibitor, additional ERK2 siRNA completely abrogated the Ro compound-dependent increase of osteoclast size. Previous reports indicated that the inhibition of ERK pathway by the treatment of osteoclast precursors with a MEK inhibitor (U0126 or PD98059) significantly suppressed the expression of Dcstamp [39,40]. Thus, potential mechanisms behind the ERK pathway-dependent enhancement of osteoclast fusion by Ro 32-3555 in current study might involve Dcstamp, considering the suggested pivotal role during the fusion of osteoclasts [9,35,40].…”

Section: Discussionsupporting

confidence: 48%

Endogenous Collagenases Regulate Osteoclast Fusion

Kim

Lee

2020

Biomolecules

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The precise regulation of osteoclast differentiation and function is crucial for the maintenance of healthy bone. Despite several reports of collagenase expression in bone tissues, the precise isoform expression as well as the role in osteoclasts are still unclear. In the present report, the expression of matrix metalloprotease (MMP)8 and MMP13 was confirmed in mouse bone marrow macrophage osteoclast precursors. The mRNA and protein expressions of both collagenases were significantly reduced by receptor activator of nuclear factor κB ligand (RANKL) stimulation. Notably, either inhibition of MMP expression by siRNA or treatment of cells with collagenase inhibitor Ro 32-3555 significantly augmented osteoclast fusion and resorption activity without affecting the osteoclast number. The inhibition of collagenase by Ro 32-3555 increased the expression of osteoclast fusion genes, Atp6v0d2 and Dcstamp, without affecting nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1) protein expression. The enhanced osteoclast fusion by collagenase inhibition appears to be mediated through an extracellular signal regulated kinase (ERK)-dependent pathway. Collectively, these data provide novel information on the regulation of osteoclast fusion process.

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Section: Discussionsupporting

confidence: 48%

Endogenous Collagenases Regulate Osteoclast Fusion

Kim

Lee

2020

Biomolecules

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“…They demonstrated that ERK1 positively regulated osteoclastogenesis, and that its disruption decreased multinucleated osteoclast formation from bone marrow mononuclear cells. A later report by Oh et al demonstrated that blockage of ERK1/2 by an ERK inhibitor significantly inhibited the expression of DC-STAMP and Atp6v0s2, and completely eliminated the formation of large, multinucleated osteoclasts [ 40 ]. In addition, two studies have shown the reciprocal regulation of endogenous and exogenous collagenases on DC-STAMP through the MAPK cascade [ 41 , 42 ].…”

Section: Dc-stampmentioning

confidence: 99%

Osteoclast Multinucleation: Review of Current Literature

Kodama

Kaito

2020

IJMS

101

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Multinucleation is a hallmark of osteoclast maturation. The unique and dynamic multinucleation process not only increases cell size but causes functional alterations through reconstruction of the cytoskeleton, creating the actin ring and ruffled border that enable bone resorption. Our understanding of the molecular mechanisms underlying osteoclast multinucleation has advanced considerably in this century, especially since the identification of DC-STAMP and OC-STAMP as “master fusogens”. Regarding the molecules and pathways surrounding these STAMPs, however, only limited progress has been made due to the absence of their ligands. Various molecules and mechanisms other than the STAMPs are involved in osteoclast multinucleation. In addition, several preclinical studies have explored chemicals that may be able to target osteoclast multinucleation, which could enable us to control pathogenic bone metabolism more precisely. In this review, we will focus on recent discoveries regarding the STAMPs and other molecules involved in osteoclast multinucleation.

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“…As previously reported, psoralen stimulates hFOB1.19 cell proliferation through activation of MAPK/ERK signaling (20). In osteoclasts, it is well established that the activation of MAPK/ERK signaling plays a key role in receptor activator of nuclear factor‐κB ligand (RANKL)‐induced osteoclast differentiation (20, 21). Meanwhile, in osteoblasts, studies have demonstrated that the activation of ERK is required for osteogenic mesenchymal stem cell differentiation and skeletal development (22, 23).…”

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confidence: 99%

Psoralen accelerates bone fracture healing by activating both osteoclasts and osteoblasts

et al. 2019

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Bone fracture healing is a complex, dynamic process that involves various cell types, with osteoclasts and osteoblasts playing indispensable roles. In this study, we found that psoralen, the main active ingredient in Psoralea corylifolia L. fruit extract, enhanced bone fracture healing through activation of osteoclast and osteoblast activity via the ERK signaling pathway. In detail, psoralen promoted receptor activator of nuclear factor‐κB ligand‐induced osteoclastogenesis, mRNA expression of osteoclast‐specific genes, and osteoclastic bone resorption in primary bone marrow‐derived macrophages. Meanwhile, psoralen induced osteogenic differentiation by promoting the mRNA expression of the osteoblast differentiation markers alkaline phosphatase, runt‐related transcription factor 2, osterix, and osteocalcin. At the molecular level, psoralen preferentially activated ERK1/2 but not JNK or p38 MAPKs. Further experiments revealed that psoralen‐induced osteoclast and osteoblast differentiation was abrogated by a specific inhibitor of phosphorylated ERK. In addition, psoralen accelerated bone fracture healing in a rat tibial fracture model, and the numbers of osteoclasts and osteoblasts were increased in psoralen‐treated fracture callus. Taken together, our findings indicate that psoralen accelerates bone fracture healing through activation of osteoclasts and osteoblasts via ERK signaling and has potential as a novel drug in the orthopedic clinic for the treatment of bone fractures.—Zhang, T., Han, W., Zhao, K., Yang, W., Lu, X., Jia, Y., Qin, A., Qian, Y. Psoralen accelerates bone fracture healing by activating both osteoclasts and osteoblasts. FASEB J. 33, 5399–5410 (2019). http://www.fasebj.org

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Obatoclax Regulates the Proliferation and Fusion of Osteoclast Precursors through the Inhibition of ERK Activation by RANKL

Cited by 16 publications

References 38 publications

Endogenous Collagenases Regulate Osteoclast Fusion

Endogenous Collagenases Regulate Osteoclast Fusion

Osteoclast Multinucleation: Review of Current Literature

Psoralen accelerates bone fracture healing by activating both osteoclasts and osteoblasts

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