Abstract
Bone homeostasis destruction is triggered by the uncontrolled activity of osteoblasts and osteoclasts. Targeting both the regulation of bone formation and resorption is a promising strategy for treating bone disorders. Cordycepin is a major component of Chinese caterpillar fungus Cordyceps militaris. It exerts a variety of biological actions in various cells and animal models. However, its function on bone metabolism remains unclear. In the present study, we discovered a dual-action function of cordycepin in murine MC3T3-E1 and RAW264.7 cells. MC3T3-E1 cells were cultured in an osteogenic medium in the presence of 1 μM cordycepin for up two weeks. Cordycepin was used for effects of osteoblast and osteoclast differentiation. Cell viability was measured using the MTT assay. Osteoblast differentiation was confirmed by alizarin red staining, ALP activity, western blot, and real-time PCR. Osteoclast differentiation and autophagic activity were confirmed via TRAP staining, pit formation assay, confocal microscopy, western blot, and real-time PCR. Cordycepin promoted osteoblast differentiation, matrix mineralization, and induction of osteoblast markers via BMP2/Runx2/Osterix pathway. On the other hand, RAW264.7 cells were differentiated into osteoclast by RANKL treatment for 72 h. 1 μM cordycepin significantly inhibited RANKL-induced osteoclast formation and resorption activity through disturbing the actin ring-formatted sealing zone and activating cathepsin K and MMP9. These findings indicate that cordycepin might be an innovative dual-action therapeutic agent for bone disease caused by an imbalance of osteoblasts and osteoclasts.
Highlights
Bone tissue is a highly dynamic central tissue and essential for the efficient execution of skeletal function
We report on the underlying mechanism by cordycepin that modulates BMP signaling-induced osteoblast differentiation in murine preosteoblastic MC3T3E1 cells and the inhibition of RANKL-induced osteoclast differentiation in murine macrophage RAW264.7 cells
To confirm the molecular mechanism of cordycepin effects on MAPKs following the activation of RANKL in RAW264.7 cells, we investigated the phosphorylation of p38, extracellular signal-regulated kinases (ERK) and Jun N-terminal kinases (JNK) using a western blot
Summary
Bone tissue is a highly dynamic central tissue and essential for the efficient execution of skeletal function. Bone homeostasis is maintained through a wellregulated balance between bone formation and bone resorption, coordinated by osteoblasts and osteoclasts, respectively [3]. An imbalance between osteoblast and osteoclast activities may trigger bone disease such as osteoporosis, osteopetrosis, Paget’s disease, and rheumatoid arthritis [4]. Osteoblasts, derived from mesenchymal stem cells, are responsible for bone formation and their functions are determined by a status of differentiation. Preosteoblastic/stromal cells, secrete RANKL (receptor activator of nuclear factor-κB ligand), which requires osteoclast differentiation, whereas mature osteoblasts develop a bone matrix through collagen synthesis and mineralization via the activation of signaling proteins and transcription factors such
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