Phillyrin Attenuates Osteoclast Formation and Function and Prevents LPS-Induced Osteolysis in Mice

Wang, Jing; Chen, Gang; Zhang, Qianqian; Zhao, Fuli; Yu, Xiaolu; Ma, Xuemei; Liu, Mei

doi:10.3389/fphar.2019.01188

Cited by 18 publications

(15 citation statements)

References 52 publications

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“…As shown in Figure 2 B,C, PL significantly inhibited osteoclastogenesis in a dose-dependent manner in vitro, as evidenced by the reduced number and average area of TRAP + multinucleated (≥3 nuclei) cells. To explore at which stage of osteoclastogenesis PL exerts its suppressive effect, we incubated BMM cells with 1 µM PL at different differentiation time points, as previously described [ 25 ]. The results showed that PL treatment on day three of the five-day culture (late treatment) and treatment on the first two days of RANKL induction (early treatment) had similar and significant inhibitory effect on osteoclast formation, both of which resulted in an approximate 30% reduction in formation of TRAP + osteoclasts ( Figure 2 D,E).…”

Section: Resultsmentioning

confidence: 99%

Piperlongumine Inhibits Titanium Particles-Induced Osteolysis, Osteoclast Formation, and RANKL-Induced Signaling Pathways

Diao

Zhang

et al. 2022

IJMS

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Wear particle-induced aseptic loosening is the most common complication of total joint arthroplasty (TJA). Excessive osteoclast formation and bone resorptive activation have been considered to be responsible for extensive bone destruction and prosthesis failure. Therefore, identification of anti-osteoclastogenesis agents is a potential therapy strategy for the treatment of aseptic loosening and other osteoclast-related osteolysis diseases. In the present study, we reported, for the first time, that piperlongumine (PL), a key alkaloid compound from Piper longum fruits, could significantly suppress the formation and activation of osteoclasts. Furthermore, PL effectively decreased the mRNA expressions of osteoclastic marker genes such as tartrate-resistant acid phosphatase (TRAP), calcitonin receptor (CTR), and cathepsin K (CTSK). In addition, PL suppressed the receptor activator of nuclear factor-κB ligand (RANKL)-induced activations of MAPKs (ERK, JNK and p38) and NF-κB, which down-regulated the protein expression of nuclear factor of activated T-cells cytoplasmic 1 (NFATc1). Using a titanium (Ti) particle-induced calvarial osteolysis model, we demonstrated that PL could ameliorate Ti particle-induced bone loss in vivo. These data provide strong evidence that PL has the potential to treat osteoclast-related diseases including periprosthetic osteolysis (PPO) and aseptic loosening.

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Section: Resultsmentioning

confidence: 99%

Piperlongumine Inhibits Titanium Particles-Induced Osteolysis, Osteoclast Formation, and RANKL-Induced Signaling Pathways

Diao

Zhang

et al. 2022

IJMS

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“…Our findings are consistent with some other reports. For example, Wang et al [ 47 , 48 ] reported that phillyrin showed a protective effect against bone loss in an in vivo model by inhibiting RANKL-induced osteoclast differentiation, but did not affect osteoblast differentiation. Interestingly, phillyrin decreased RANKL expression in an in vivo model of osteolysis.…”

Section: Discussionmentioning

confidence: 99%

N-[2-(4-Acetyl-1-Piperazinyl)Phenyl]-2-(3-Methylphenoxy)Acetamide (NAPMA) Inhibits Osteoclast Differentiation and Protects against Ovariectomy-Induced Osteoporosis

et al. 2020

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Osteoclasts are large, multinucleated cells responsible for bone resorption and are induced in response to the regulatory activity of receptor activator of nuclear factor-kappa B ligand (RANKL). Excessive osteoclast activity causes pathological bone loss and destruction. Many studies have investigated molecules that specifically inhibit osteoclast activity by blocking RANKL signaling or bone resorption. In recent years, we screened compounds from commercial libraries to identify molecules capable of inhibiting RANKL-induced osteoclast differentiation. Consequently, we reported some compounds that are effective at attenuating osteoclast activity. In this study, we found that N-[2-(4-acetyl-1-piperazinyl)phenyl]-2-(3-methylphenoxy)acetamide (NAPMA) significantly inhibited the formation of multinucleated tartrate-resistant acid phosphatase (TRAP)-positive cells from bone marrow-derived macrophages in a dose-dependent manner, without cytotoxic effects. NAPMA downregulated the expression of osteoclast-specific markers, such as c-Fos, NFATc1, DC-STAMP, cathepsin K, and MMP-9, at the transcript and protein levels. Accordingly, bone resorption and actin ring formation were decreased in response to NAPMA treatment. Furthermore, we demonstrated the protective effect of NAPMA against ovariectomy-induced bone loss using micro-CT and histological analysis. Collectively, the results showed that NAPMA inhibited osteoclast differentiation and attenuated bone resorption. It is thus a potential drug candidate for the treatment of osteoporosis and other bone diseases associated with excessive bone resorption.

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“…Phillyrin, an active ingredient extracted from forsythia, significantly inhibited receptor activator of nuclear factor κB ligand (RANKL)-induced osteoclastogenesis and bone resorption in vitro and protected against lipopolysaccharide-induced osteolysis in vivo. Phillyrin effectively blocked RANKL-induced activations of c-Jun N-terminal kinase and extracellular signal-regulated kinase, which suppressed the expression of c-Fos and nuclear factor of activated T-cells cytoplasmic 1 [15]. Imperatorin (IMT) reduced the release of TNF-α, IL-6 and IL-1β, inhibited the expression of iNOS and COX-2, and suppressed the activity of NF-κB via upregulation of the expression of p65 (C) and IκB (C), and downregulation of the expression of p65 (N) [16].…”

Section: Chemical Constituents Of "Sanse Powder" Prescriptionmentioning

confidence: 99%

Interventional effects of the direct application of “Sanse powder” on knee osteoarthritis in rats as determined from lipidomics via UPLC-Q-Exactive Orbitrap MS

Huang

Shan

et al. 2020

Chin Med

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Background: Our previous clinical evidence suggested that the direct application of "Sanse powder" the main ingredient of "Yiceng" might represent an alternative treatment for knee osteoarthritis. However, the mechanism underlying its effect is poorly understood. In this study, we investigated the mechanism of the effect of direct "Sanse powder" application for the treatment of knee osteoarthritis (KOA) in rats by using lipidomics. Methods: KOA rats were established by cutting the anterior cruciate ligament, and the cold pain threshold and mechanical withdrawal threshold (MWT) of seven rats from each group were measured before modelling (0 days) and at 7, 14, 21 and 28 days after modelling. Histopathological evaluation of the synovial tissue was performed by haematoxylin and eosin (H&E) staining after modelling for 28 days. Interleukin-1β (IL-1β), pro-interleukin-1β (pro-IL-1β) and tumor necrosis factor-α (TNF-α) proteins in synovial tissue were measured by western blot, and the mRNA expression levels of IL-1β and TNF-α in synovial tissue were measured using Real-time reverse transcription polymerase chain reaction (qRT-PCR), the levels of IL-1β and TNF-α in rat serum were measured by enzyme-linked immunosorbent assay (ELISA), Serum lipid profiles were obtained by using ultra-performance liquid chromatography combined with quadrupole-Exactive Orbitrap mass spectrometry (UPLC-Q-Exactive Orbitrap MS). Results: The results confirmed that the direct application of "Sanse powder" had a significant protective effect against KOA in rats. Treatment with "Sanse powder" not only attenuated synovial tissue inflammation but also increased the levels of the cold pain threshold and MWT. In addition, the lipidomics results showed that the levels of diacylglycerol (DAG), triacylglycerols (TAGs), lysophosphatidylcholine (LPC), phosphatidylcholine (PC), fatty acid esters of hydroxy fatty acids (FAHFAs), and phosphatidylethanolamine (PE) were restored almost to control levels following treatment. Conclusions: Lipidomics provides a better understanding of the actions of direct application "Sanse powder" therapy for KOA.

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Phillyrin Attenuates Osteoclast Formation and Function and Prevents LPS-Induced Osteolysis in Mice

Cited by 18 publications

References 52 publications

Piperlongumine Inhibits Titanium Particles-Induced Osteolysis, Osteoclast Formation, and RANKL-Induced Signaling Pathways

Piperlongumine Inhibits Titanium Particles-Induced Osteolysis, Osteoclast Formation, and RANKL-Induced Signaling Pathways

N-[2-(4-Acetyl-1-Piperazinyl)Phenyl]-2-(3-Methylphenoxy)Acetamide (NAPMA) Inhibits Osteoclast Differentiation and Protects against Ovariectomy-Induced Osteoporosis

Interventional effects of the direct application of “Sanse powder” on knee osteoarthritis in rats as determined from lipidomics via UPLC-Q-Exactive Orbitrap MS

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