Psoralen accelerates bone fracture healing by activating both osteoclasts and osteoblasts

Zhang, Tan; Han, Weiqi; Zhao, Kai; Yang, Wanlei; Lu, Xuanyuan; Jia, Yewei; Qin, An; Qian, Yu

doi:10.1096/fj.201801797r

Cited by 48 publications

(39 citation statements)

References 53 publications

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“…Accordingly, coumarin may ameliorate diabetic dysfunction of osteoclastogenesis concomitantly with optimal enzymatic activity at the low pH during the acidification of resorption lacuna. A recent study reported that psoralen accelerates bone fracture healing through activation of both osteoclasts and osteoblasts via preferential signaling of ERK, but not JNK or p38 MAPK [41].…”

Section: Discussionmentioning

confidence: 99%

Coumarin Ameliorates Impaired Bone Turnover by Inhibiting the Formation of Advanced Glycation End Products in Diabetic Osteoblasts and Osteoclasts

et al. 2020

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Accumulating evidence demonstrates that the risk of osteoporotic fractures increases in patients with diabetes mellitus. Thus, diabetes-induced bone fragility has recently been recognized as a diabetic complication. As the fracture risk is independent of the reduction in bone mineral density, deterioration in bone quality may be the main cause of bone fragility. Coumarin exists naturally in many plants as phenylpropanoids and is present in tonka beans in significantly high concentrations. This study investigated whether coumarin ameliorated the impaired bone turnover and remodeling under diabetic condition. The in vitro study employed murine macrophage Raw 264.7 cells differentiated to multinucleated osteoclasts with receptor activator of nuclear factor-κΒ ligand (RANKL) in the presence of 33 mM glucose and 1–20 μM coumarin for five days. In addition, osteoblastic MC3T3-E1 cells were exposed to 33 mM glucose for up to 21 days in the presence of 1–20 μM coumarin. High glucose diminished tartrate-resistant acid phosphatase activity and bone resorption in RANKL-differentiated osteoclasts, accompanying a reduction of cathepsin K induction and actin ring formation. In contrast, coumarin reversed the defective osteoclastogenesis in diabetic osteoclasts. Furthermore, high glucose diminished alkaline phosphatase activity and collagen type 1 induction of osteoblasts, which was strongly enhanced by submicromolar levels of coumarin to diabetic cells. Furthermore, coumarin restored the induction of RANK and osteoprotegerin in osteoclasts and osteoblasts under glucotoxic condition, indicating a tight coupling of osteoclastogenesis and osteoblastogenesis. Coumarin ameliorated the impaired bone turnover and remodeling in diabetic osteoblasts and osteoclasts by suppressing the interaction between advanced glycation end product (AGE) and its receptor (RAGE). Therefore, coumarin may restore optimal bone turnover of osteoclasts and osteoblasts by disrupting the hyperglycemia-mediated AGE–RAGE interaction.

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Section: Discussionmentioning

confidence: 99%

Coumarin Ameliorates Impaired Bone Turnover by Inhibiting the Formation of Advanced Glycation End Products in Diabetic Osteoblasts and Osteoclasts

et al. 2020

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“…Unexpectedly, the ERK signaling pathway was significantly inhibited by IMD 0354, which has not been reported previously. The ERK signaling pathway is involved in many biological processes, including the regulation of inflammation, cell proliferation, and cell differentiation 34,35 .…”

Section: Discussionmentioning

confidence: 99%

The emerging role of IMD 0354 on bone homeostasis by suppressing osteoclastogenesis and bone resorption, but without affecting bone formation

et al. 2019

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Osteoporosis is caused by an imbalance between bone formation and bone resorption. Receptor activator of nuclear factor-κB ligand (RANKL) promotes the activity and differentiation of osteoclasts via activating the nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways. IMD 0354 is a selective molecular inhibitor of inhibitor of NF-κB kinase subunit beta (IKKβ) and effective for treatment of acute and subacute inflammatory diseases through the suppression of NF-κB activation. However, the effect of IMD 0354 on bone homeostasis is unknown. In this study, we demonstrated that IMD 0354 significantly attenuated ovariectomy-induced bone loss and inhibited osteoclastogenesis in mice, whereas bone formation was not affected. Additionally, IMD 0354 dramatically inhibited osteoclast differentiation and function induced by RANKL and macrophage colony-stimulating factor in bone marrow monocytes as verified by tartrate-resistant acid phosphatase (TRAP) staining as well as bone resorption assay in vitro. Subsequently, we found that activation of NF-κB signaling and the ERK/c-Fos axis were blunted during osteoclast formation induced by RANKL. Transcription factors nuclear factor of activated T cells c1 (NFATc1) and c-Fos were suppressed with the decreased expression of osteoclast-related genes by IMD 0354. Our findings suggest that IMD 0354 could be a potential preventive and therapeutic drug for osteoporosis.

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“…However, the effect of psoralen on the phosphorylation of ASK1, JNK, and MAPK P38 in osteoblasts and osteoclasts remains controversial and requires further study (Li F. et al, 2017;Chen et al, 2017a;Chai et al, 2018;Zhang et al, 2019).…”

Section: Clinical Researchmentioning

confidence: 99%

“…Based on the complementary actions of osteoclasts and osteoblasts, Zhang et al demonstrated that psoralen is able to promote osteoclast differentiation by activating ERK signals which could also promote osteoblast differentiation, That is, psoralen can enhance the viability of osteoblasts and osteoclasts by activating the ERK signaling pathway, thereby promoting fracture healing. In addition, osteoclast and osteoblast differentiation induced by psoralen can be inhibited by a specific inhibitor of phosphorylated ERK (Zhang et al, 2019).…”

Section: Effects On Osteoblasts and Osteoclastsmentioning

confidence: 99%

A Review of the Pharmacological Properties of Psoralen

et al. 2020

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Psoralen is the principal bioactive component in the dried fruits of Cullen corylifolium (L.) Medik (syn. Psoralea corylifolia L), termed "Buguzhi" in traditional Chinese medicine (TCM). Recent studies have demonstrated that psoralen displays multiple bioactive properties, beneficial for the treatment of osteoporosis, tumors, viruses, bacteria, and inflammation. The present review focuses on the research evidence relating to the properties of psoralen gathered over recent years. Firstly, multiple studies have demonstrated that psoralen exerts strong anti-osteoporotic effects via regulation of osteoblast/osteoclast/chondrocyte differentiation or activation due to the participation in multiple molecular mechanisms of the wnt/b-catenin, bone morphogenetic protein (BMP), inositol-requiring enzyme 1 (IRE1)/ apoptosis signaling kinase 1 (ASK1)/c-jun N-terminal kinase (JNK) and the Protein Kinase B (AKT)/activator protein-1 (AP-1) axis, and the expression of miR-488, peroxisome proliferators-activated receptor-gamma (PPARg), and matrix metalloproteinases (MMPs). In addition, the antitumor properties of psoralen are associated with the induction of ER stress-related cell death via enhancement of PERK: Pancreatic Endoplasmic Reticulum Kinase (PERK)/activating transcription factor (ATF), 78kD glucose-regulated protein (GRP78)/C/EBP homologous protein (CHOP), and 94kD glucose-regulated protein (GRP94)/CHOP signaling, and inhibition of P-glycoprotein (P-gp) or ATPase that overcomes multidrug resistance. Furthermore, multiple articles have shown that the antibacterial, anti-inflammatory and neuroprotective effects of psoralen are a result of its interaction with viral polymerase (Pol), destroying the formation of biofilm, and regulating the activation of tumor necrosis factor alpha (TNF-a), transforming growth factor beta (TGF-b), interleukin 4

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Psoralen accelerates bone fracture healing by activating both osteoclasts and osteoblasts

Cited by 48 publications

References 53 publications

Coumarin Ameliorates Impaired Bone Turnover by Inhibiting the Formation of Advanced Glycation End Products in Diabetic Osteoblasts and Osteoclasts

Coumarin Ameliorates Impaired Bone Turnover by Inhibiting the Formation of Advanced Glycation End Products in Diabetic Osteoblasts and Osteoclasts

The emerging role of IMD 0354 on bone homeostasis by suppressing osteoclastogenesis and bone resorption, but without affecting bone formation

A Review of the Pharmacological Properties of Psoralen

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