PMSA prevents osteoclastogenesis and estrogen-dependent bone loss in mice

Cho, Eunjin; Chen, Zhihao; Ding, Mina; Seong, Jihyoun; Lee, Sunwoo; Min, Sang Hyun; Choi, Dong Kyu; Lee, Tae‐Hoon

doi:10.1016/j.bone.2020.115707

Cited by 12 publications

(33 citation statements)

References 30 publications

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“…RNA was isolated from BMMs, SNCs, and MNCs, and qRT-PCR was performed as described previously [ 11 ]. Briefly, RNA was isolated using an RNeasy kit (Qiagen, Hilden, Germany), and cDNA was synthesized using a Prime Script RT reagent kit (Takara, Kusatsu, Shiga, Japan) following the manufacturer’s instructions.…”

Section: Methodsmentioning

confidence: 99%

“…Osteoclasts were imaged using a Carl Zeiss microscope (Carl Zeiss, Jena, Germany). Protein isolation and Western blotting were performed as previously described [ 11 ]. A polyclonal Calcrl antibody (Sigma-Aldrich, St. Louis, MO, USA) was used for immunostaining and Western blotting.…”

Section: Methodsmentioning

confidence: 99%

“…RANKL binds to the RANK receptor on the surfaces of osteoclast precursors to activate downstream signaling pathways, including the mitogen-activated protein kinase and Akt pathways, and transcription factors, such as NF-κB, activator protein 1, microphthalmia-associated transcription factor (MITF), c-Fos, and nuclear factor of activated T-cell cytoplasmic-1 (NFATc1) [ 8 , 9 , 10 ]. These transcription factors promote the expression of osteoclastogenic genes, such as tartrate-resistant acid phosphatase ( TRAP , Acp5 ), v-ATPase subunit d2 ( Atp6v0d2 ), cathepsin K ( Ctsk ), osteoclast-associated receptor ( Oscar ), osteoclast stimulatory transmembrane protein ( OC-STAMP ), and dendritic cell-specific transmembrane protein ( DC-STAMP ) [ 11 ].…”

Section: Introductionmentioning

confidence: 99%

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Identification of Novel Genes for Cell Fusion during Osteoclast Formation

Cho

Cheon²,

Ding³

et al. 2022

IJMS

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Osteoclasts are derived from hematopoietic stem cells. Monocyte preosteoclasts obtain resorbing activity via cell–cell fusion to generate multinucleated cells. However, the mechanisms and molecules involved in the fusion process are poorly understood. In this study, we performed RNA sequencing with single nucleated cells (SNCs) and multinucleated cells (MNCs) to identify the fusion-specific genes. The SNCs and MNCs were isolated under the same conditions during osteoclastogenesis with the receptor activator of nuclear factor-κB ligand (RANKL) administration. Based on this analysis, the expression of seven genes was found to be significantly increased in MNCs but decreased in SNCs, compared to that in bone marrow-derived macrophages (BMMs). We then generated knockout macrophage cell lines using a CRISPR-Cas9 genome-editing tool to examine their function during osteoclastogenesis. Calcrl-, Marco-, or Ube3a-deficient cells could not develop multinucleated giant osteoclasts upon RANKL stimulation. However, Tmem26-deficient cells fused more efficiently than control cells. Our findings demonstrate that Calcrl, Marco, and Ube3a are novel determinants of osteoclastogenesis, especially with respect to cell fusion, and highlight potential targets for osteoporosis therapy.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Identification of Novel Genes for Cell Fusion during Osteoclast Formation

Cho

Cheon²,

Ding³

et al. 2022

IJMS

Self Cite

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“… 32 Accumulating evidence indicates that receptor activator for nuclear factor kappa-B ligand (RANKL) accelerates the formation of osteoclasts, resulting in severe bone erosion and cartilage degradation. 33 IL-17 and TNF-α in synovial fibroblasts greatly enhance RANKL expression. In a RANKL transgenic mice model, a distinct reduction in bone mass was exhibited, caused by a rise in the osteoclast number.…”

Section: Dysregulated Immune Homeostasis In Ramentioning

confidence: 95%

Cell-based therapies for rheumatoid arthritis: opportunities and challenges

Chen

2022

Therapeutic Advances in Musculoskeletal

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Rheumatoid arthritis (RA) is the most common immune-mediated inflammatory disease characterized by chronic synovitis that hardly resolves spontaneously. The current treatment of RA consists of nonsteroidal anti-inflammatory drugs (NSAIDs), glucocorticoids, conventional disease-modifying antirheumatic drugs (cDMARDs), biologic and targeted synthetic DMARDs. Although the treat-to-target strategy has been intensively applied in the past decade, clinical unmet needs still exist since a substantial proportion of patients are refractory or even develop severe adverse effects to current therapies. In recent years, with the deeper understanding of immunopathogenesis of the disease, cell-based therapies have exhibited effective and promising interventions to RA. Several cell-based therapies, such as mesenchymal stem cells (MSC), adoptive transfer of regulatory T cells (Treg), and chimeric antigen receptor (CAR)-T cell therapy as well as their beneficial effects have been documented and verified so far. In this review, we summarize the current evidence and discuss the prospect as well as challenges for these three types of cellular therapies in RA.

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“…Osteoporosis is characterized by a decrease in the amount of bone tissue per unit volume and mainly occurs in postmenopausal women and diabetes patients ( Chapurlat et al, 2020 ; Zhou et al, 2020 ). Estrogen deficiency and glucose overload reduce the inhibition of osteoclast differentiation and enhances bone resorption, leading to the loss of bone mass ( Ponte et al, 2020 ; Cho et al, 2021 ; Sha et al, 2021 ). The current strategy for osteoporosis treatment is mainly to inhibit osteoclasts with drugs such as bisphosphonates, estrogen receptor modulators and calcitonin ( Ukon et al, 2019 ; Hsiao et al, 2020 ; Toriumi et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

Metformin Promotes Differentiation and Attenuates H2O2-Induced Oxidative Damage of Osteoblasts via the PI3K/AKT/Nrf2/HO-1 Pathway

et al. 2022

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At present, the drug treatment of osteoporosis is mostly focused on inhibiting osteoclastogenesis, which has relatively poor effects. Metformin is a drug that can potentially promote osteogenic differentiation and improve bone mass in postmenopausal women. We aimed to detect the molecular mechanism underlying the osteogenic effect of metformin. Our study indicated that metformin obviously increased the Alkaline phosphatase activity and expression of osteogenic marker genes at the mRNA and protein levels. The PI3K/AKT signaling pathway was revealed to play an essential role in the metformin-induced osteogenic process, as shown by RNA sequencing. We added LY294002 to inhibit the PI3K/AKT pathway, and the results indicated that the osteogenic effect of metformin was also blocked. Additionally, the sequencing data also indicated oxidation-reduction reaction was involved in the osteogenic process of osteoblasts. We used H2O2 to mimic the oxidative damage of osteoblasts, but metformin could attenuate it. Antioxidative Nrf2/HO-1 pathway, regarded as the downstream of PI3K/AKT pathway, was modulated by metformin in the protective process. We also revealed that metformin could improve bone mass and oxidative level of OVX mice. In conclusion, our study revealed that metformin promoted osteogenic differentiation and H2O2-induced oxidative damage of osteoblasts via the PI3K/AKT/Nrf2/HO-1 pathway.

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PMSA prevents osteoclastogenesis and estrogen-dependent bone loss in mice

Cited by 12 publications

References 30 publications

Identification of Novel Genes for Cell Fusion during Osteoclast Formation

Identification of Novel Genes for Cell Fusion during Osteoclast Formation

Cell-based therapies for rheumatoid arthritis: opportunities and challenges

Metformin Promotes Differentiation and Attenuates H2O2-Induced Oxidative Damage of Osteoblasts via the PI3K/AKT/Nrf2/HO-1 Pathway

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