Abstract

Persimmon (Diospyros kaki L.f.) leaves have traditionally been used as a phytomedicine, in health beverages to treat cardiovascular and respiratory disease and to promote maternal health in East Asia. In particular, polysaccharides from persimmon are known to have anti-coagulant, anti-oxidant, and immune-stimulatory activities. However, their beneficial effects against osteoporosis have not been reported. In the present study, we investigated the anti-osteoporotic effects of polysaccharides from persimmon leaves (PLE0) using an in vivo model of ovariectomy (OVX)-induced bone loss and an in vitro system of receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast differentiation. In the OVX mouse model, PLE0 remarkably improved OVX-induced trabecular bone loss by suppressing osteoclast activity. In primary bone marrow-derived macrophages (BMMs), PLE0 dose-dependently inhibited osteoclast differentiation. In addition, PLE0 down-regulated RANKL-induced activation of mitogen-activated protein kinases (MAPKs) such as p38, ERK, and JNK resulting in suppression of nuclear factor of activated T cells cytoplasmic 1 (NFATc1) expression. Our results indicate that PLE0 has anti-osteoporotic effects in OVX-induced bone loss via inhibition of osteoclast differentiation. Taken together, PLE0 from persimmon may prevent postmenopausal bone loss and osteoporotic bone fragility.

Highlights

  • IntroductionBone remodeling is tightly regulated via coupling and communication between osteoblasts (bone-forming cells) and osteoclasts (bone-resorbing cells)

  • Bone remodeling is tightly regulated via coupling and communication between osteoblasts and osteoclasts

  • We investigated the effect of polysaccharides from persimmon leaves (PLE0) in ameliorating in vivo osteoporotic bone loss and inhibiting in vitro osteoclast differentiation

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Summary

Introduction

Bone remodeling is tightly regulated via coupling and communication between osteoblasts (bone-forming cells) and osteoclasts (bone-resorbing cells). Osteoclasts are multinucleated giant cells formed via proliferation, differentiation, and fusion of mononuclear hematopoietic progenitor cells During these processes, macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor-κB ligand (RANKL) have pivotal roles in osteoclast formation and activation [2,3]. RANKL, as a key regulator of osteoclast differentiation, triggers the activation of the mitogen-activated protein kinases (MAPKs) and the canonical nuclear factor-κB (NF-κB) pathway through binding to its receptor, RANK. These processes up-regulate expression of NFATc1, a master transcription factor of RANKL-induced osteoclast differentiation [4]. Previous reports demonstrated that ectopic expression of NFATc1 causes precursors

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