IL1β and TNFα promote RANKL-dependent adseverin expression and osteoclastogenesis

Wang, Yongqiang; Galli, Matthew; Silver, Alexandra Shade; Wilson, Lionel; Song, Yushan; Mei, Yixue Michelle; Bachus, Carly; Glogauer, Michael; McCulloch, Christopher A.

doi:10.1242/jcs.213967

Cited by 17 publications

(9 citation statements)

References 69 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition to the effects on BMSC senescence and osteogenesis, the upregulation of SASP inflammatory factors may also promote osteoclastogenesis. For example, IL1, IL6, IL8, and MCSF contribute to osteoclast formation and activity (Briot et al 2017, Wang et al 2018. In our experiments, osteoclastogenesis enhancement in OVX mice was confirmed, and the in vivo injection of a JAK inhibitor reduced the number of osteoclasts on the bone surface (Supplementary Fig.…”

Section: Journal Of Endocrinologysupporting

confidence: 65%

JAK2/STAT3 regulates estrogen-related senescence of bone marrow stem cells

et al. 2020

Journal of Endocrinology

View full text Add to dashboard Cite

Emerging evidence has indicated that estrogen deficiency contributes to osteoporosis by affecting the level of inflammation. The inflammation microenvironment affects many cellular physiological processes, one of which may be cellular senescence according to previous studies. Senescent cells cannot function normally and secrete inflammatory cytokines and degradative proteins, which are referred to as senescence-associated secretory phenotype (SASP) factors, inducing further senescence and inflammation. Thus, stopping this vicious cycle may be helpful for postmenopausal osteoporosis treatment. Here, we used ovariectomized (OVX) mice as an estrogen-deficient model and confirmed that OVX bone marrow mesenchymal stem cells (BMSCs) displayed a senescent phenotype and upregulated SASP factor secretion both in vitro and in vivo. Furthermore, JAK2/STAT3, an important cytokine secretion-related signalling pathway that is associated with SASP secretion, was activated. Estrogen addition and estrogen receptor blockade confirmed that the JAK2/STAT3 axis participated in OVX BMSC senescence by mediating SASP factors. And JAK inhibition reduced SASP factor expression, alleviated senescence and enhanced osteogenic differentiation. Intraperitoneal injection of a JAK inhibitor, ruxolitinib, prevented bone loss in OVX mice. Collectively, our results revealed that JAK2/STAT3 plays an important role in the inflammation-senescence-SASP feedback loop in OVX BMSCs and that JAK inhibition could be a new method for treating postmenopausal osteoporosis.

show abstract

Section: Journal Of Endocrinologysupporting

confidence: 65%

JAK2/STAT3 regulates estrogen-related senescence of bone marrow stem cells

et al. 2020

Journal of Endocrinology

View full text Add to dashboard Cite

show abstract

“…Hence, defects in the migration of precursors results in a decreased OCL fusion. These molecules include Rac2 [ 86 ], adseverin [ 126 ], and LIM1 [ 127 ]. A force-generating molecule, Myosin X, is known to be also involved in the migration of the precursors [ 128 ].…”

Section: Multiple Roles Of the Actin Cytoskeleton In Phagocyte Mulmentioning

confidence: 99%

Heterogeneity and Actin Cytoskeleton in Osteoclast and Macrophage Multinucleation

Takito

Nakamura

2020

IJMS

View full text Add to dashboard Cite

Osteoclast signatures are determined by two transcriptional programs, the lineage-determining transcription pathway and the receptor activator of nuclear factor kappa-B ligand (RANKL)-dependent differentiation pathways. During differentiation, mononuclear precursors become multinucleated by cell fusion. Recently, live-cell imaging has revealed a high level of heterogeneity in osteoclast multinucleation. This heterogeneity includes the difference in the differentiation states and the mobility of the fusion precursors, as well as the mode of fusion among the fusion precursors with different numbers of nuclei. In particular, fusion partners often form morphologically distinct actin-based linkages that allow two cells to exchange lipids and proteins before membrane fusion. However, the origin of this heterogeneity remains elusive. On the other hand, osteoclast multinucleation is sensitive to the environmental cues. Such cues promote the reorganization of the actin cytoskeleton, especially the formation and transformation of the podosome, an actin-rich punctate adhesion. This review covers the heterogeneity of osteoclast multinucleation at the pre-fusion stage with reference to the environment-dependent signaling pathway responsible for reorganizing the actin cytoskeleton. Furthermore, we compare osteoclast multinucleation with macrophage fusion, which results in multinucleated giant macrophages.

show abstract

“…Previous published studies have revealed that although IL-1 can activate osteoclast maturation and enhance bone resorption, it alone cannot initiate the process of osteoclast differentiation from osteoclast precursors (18,19). Kim et al (20) however, suggested that IL-1 can induce osteoclast differentiation without the interaction of RANKL/RANK in the context of appropriate microenvironmental conditions.…”

Section: Introductionmentioning

confidence: 99%

Interleukin‑1 induces receptor activator of nuclear factor‑κB ligand‑independent osteoclast differentiation in RAW264.7 cells

Liao

Feng

et al. 2021

Exp Ther Med

View full text Add to dashboard Cite

Interleukin-1 (IL-1) is a pro-inflammatory cytokine which induces bone destruction in various diseases, such as osteoporosis and rheumatoid arthritis. RAW264.7 cells are frequently used in studies as osteoclast precursors, however it remains unclear whether IL-1 can induce osteoclast differentiation from RAW264.7 cells without the stimulation of receptor activator of nuclear factor-κB ligand (RANKL). Hence, the present study aimed to investigate the effects of IL-1 on the formation of osteoclasts from RAW264.7 cells. The cell viability was determined via the Cell Counting Kit-8 (CCK-8) assay. Protein and gene expression were measured by western blotting and reverse transcription-quantitative PCR, respectively. Tartrate-resistant acid phosphatase (TRAP) staining and the resorption pit assay were performed to determine the formation and activity of osteoclasts. A significantly increased quantity of osteoclasts were found in the IL-1 group compared with the control group, and also in the RANKL+IL-1 group compared with the RANKL group. In addition IL-1 significantly increased both the protein and mRNA expression of specific genes associated with osteoclastogenesis, including nuclear factor of activated T cells cytoplasmic 1, matrix metalloprotein-9, cathepsin K and TRAP. The findings of the present study suggested that IL-1 can induce osteoclast differentiation and upregulate the quantity of osteoclasts differentiated from RAW264.7 cells. These results may lay a foundation for further study of diseases involving inflammation-associated bone loss.The combined blockade of IL-1 and RANKL may be effective for the prevention of inflammatory bone loss.

show abstract

IL1β and TNFα promote RANKL-dependent adseverin expression and osteoclastogenesis

Cited by 17 publications

References 69 publications

JAK2/STAT3 regulates estrogen-related senescence of bone marrow stem cells

JAK2/STAT3 regulates estrogen-related senescence of bone marrow stem cells

Heterogeneity and Actin Cytoskeleton in Osteoclast and Macrophage Multinucleation

Interleukin‑1 induces receptor activator of nuclear factor‑κB ligand‑independent osteoclast differentiation in RAW264.7 cells

Contact Info

Product

Resources

About