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Title: Pilose antler peptide potentiates osteoblast differentiation and inhibits osteoclastogenesis via manipulating the NF-κB pathway

Abstract

Bones are inflexible yet ever-changing metabolic organs, and bone homeostasis is maintained through two delicately regulated processes: bone construction and bone reabsorption. An imbalance in bone metabolism is linked to most orthopedic diseases, including osteoporosis and rheumatoid arthritis. Importantly, tumor necrosis factor-α (TNF-α) blocks osteoblast differentiation and stimulates osteoclast formation, resulting in delayed deposition of new bone and accelerated bone resorption, especially in rheumatoid arthritis patients with inflammatory conditions. Pilose antler peptide (PAP) isolated and purified from deer antlers has been shown to have beneficial effects on chronic inflammation. In the present study, we studied the impact of PAP on osteoblast differentiation and evaluated the regulatory mechanism, with particular emphasis on the effect of PAP on TNF-α-mediated NF-κB signaling. Mouse primary osteoblast cells were activated with bone morphogenetic protein-2 (BMP-2) for osteoblast differentiation. A significant stimulatory effect of PAP in osteoblastogenesis was observed using ALP activity and Alizarin Red S staining assays. Meanwhile, PAP significantly rescued TNF-α-induced impairment of osteoblast formation as well as mineralization. Furthermore, we found a similar trend upon analyzing osteoblast-specific gene expression. PAP significantly rescued TNF-α-mediated decrease in expression of osteoblast-specific genes. A molecular mechanism assay indicated that PAP significantly inhibited TNF-α-mediated stimulation of NF-κB signalingmore » activity, as well as nuclear translocation of its subunit p65. Moreover, over-expression of p65 reversed the stimulatory effects of PAP on osteoblast differentiation. Furthermore, we also identified that PAP dose dependently inhibit osteoclastogenesis, and this effect might be achieved via suppressing NF-κB activity. In summary, this study shows that PAP promotes osteoblast differentiation and blocks TNF-α-mediated suppression of osteoblastogenesis in vitro via the NF-κB/p65 pathway, as well as inhibits osteoclastsogenesis in vitro. Therefore, PAP, a novel drug with both antiresorptive and osteoanabolic activity, shows therapeutic potential as an alternative treatment for osteolytic diseases, including rheumatoid arthritis and osteoporosis. - Highlights: • PAP promotes osteoblasts differentiation and inhibits osteoclastogenesis. • PAP blocks TNFα-mediated suppression of osteoblastogenesis via NF-κB pathway. • PAP shows both antiresorptive and osteoanabolic activity, and is promising in the treatment of inflammatory bone loss.« less

Authors:
 [1];  [2]; ; ;  [3];  [4];  [5]; ;  [4]; ; ; ; ;  [3];  [1]
  1. Department of Orthopaedics, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu (China)
  2. (China)
  3. Department of Orthopaedics, Xuzhou Central Hospital, Xuzhou Clinical School of Xuzhou Medical University, The Affiliated XuZhou Hospital of Medical College of Southeast University, Xuzhou Clinical Medical College of Nanjing University of Chinese Medicine, Xuzhou, Jiangsu (China)
  4. Department of Orthopaedics, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai (China)
  5. Department of Orthopaedics, Shanghai Sixth People's Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai (China)
Publication Date:
OSTI Identifier:
22719079
Resource Type:
Journal Article
Journal Name:
Biochemical and Biophysical Research Communications
Additional Journal Information:
Journal Volume: 491; Journal Issue: 2; Other Information: Copyright (c) 2017 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0006-291X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ALIZARIN; ANTLERS; CONNECTIVE TISSUE CELLS; DEER; GENES; HOMEOSTASIS; IN VITRO; INFLAMMATION; INHIBITION; METABOLISM; MICE; MINERALIZATION; NECROSIS; NEOPLASMS; OSTEOPOROSIS; PEPTIDES; RHEUMATIC DISEASES; SKELETON

Citation Formats

Liu, Guangwang, Department of Orthopaedics, Xuzhou Central Hospital, Xuzhou Clinical School of Xuzhou Medical University, The Affiliated XuZhou Hospital of Medical College of Southeast University, Xuzhou Clinical Medical College of Nanjing University of Chinese Medicine, Xuzhou, Jiangsu, Ma, Chao, Wang, Peian, Zhang, Peiying, Qu, Xinhua, Liu, Shen, Zhai, Zanjing, Yu, Degang, Gao, Juan, Liang, Jun, Dai, Weixiang, Zhou, Lindong, Xia, Mengjiao, and Yang, Huilin. Pilose antler peptide potentiates osteoblast differentiation and inhibits osteoclastogenesis via manipulating the NF-κB pathway. United States: N. p., 2017. Web. doi:10.1016/J.BBRC.2017.07.091.
Liu, Guangwang, Department of Orthopaedics, Xuzhou Central Hospital, Xuzhou Clinical School of Xuzhou Medical University, The Affiliated XuZhou Hospital of Medical College of Southeast University, Xuzhou Clinical Medical College of Nanjing University of Chinese Medicine, Xuzhou, Jiangsu, Ma, Chao, Wang, Peian, Zhang, Peiying, Qu, Xinhua, Liu, Shen, Zhai, Zanjing, Yu, Degang, Gao, Juan, Liang, Jun, Dai, Weixiang, Zhou, Lindong, Xia, Mengjiao, & Yang, Huilin. Pilose antler peptide potentiates osteoblast differentiation and inhibits osteoclastogenesis via manipulating the NF-κB pathway. United States. doi:10.1016/J.BBRC.2017.07.091.
Liu, Guangwang, Department of Orthopaedics, Xuzhou Central Hospital, Xuzhou Clinical School of Xuzhou Medical University, The Affiliated XuZhou Hospital of Medical College of Southeast University, Xuzhou Clinical Medical College of Nanjing University of Chinese Medicine, Xuzhou, Jiangsu, Ma, Chao, Wang, Peian, Zhang, Peiying, Qu, Xinhua, Liu, Shen, Zhai, Zanjing, Yu, Degang, Gao, Juan, Liang, Jun, Dai, Weixiang, Zhou, Lindong, Xia, Mengjiao, and Yang, Huilin. Sat . "Pilose antler peptide potentiates osteoblast differentiation and inhibits osteoclastogenesis via manipulating the NF-κB pathway". United States. doi:10.1016/J.BBRC.2017.07.091.
@article{osti_22719079,
title = {Pilose antler peptide potentiates osteoblast differentiation and inhibits osteoclastogenesis via manipulating the NF-κB pathway},
author = {Liu, Guangwang and Department of Orthopaedics, Xuzhou Central Hospital, Xuzhou Clinical School of Xuzhou Medical University, The Affiliated XuZhou Hospital of Medical College of Southeast University, Xuzhou Clinical Medical College of Nanjing University of Chinese Medicine, Xuzhou, Jiangsu and Ma, Chao and Wang, Peian and Zhang, Peiying and Qu, Xinhua and Liu, Shen and Zhai, Zanjing and Yu, Degang and Gao, Juan and Liang, Jun and Dai, Weixiang and Zhou, Lindong and Xia, Mengjiao and Yang, Huilin},
abstractNote = {Bones are inflexible yet ever-changing metabolic organs, and bone homeostasis is maintained through two delicately regulated processes: bone construction and bone reabsorption. An imbalance in bone metabolism is linked to most orthopedic diseases, including osteoporosis and rheumatoid arthritis. Importantly, tumor necrosis factor-α (TNF-α) blocks osteoblast differentiation and stimulates osteoclast formation, resulting in delayed deposition of new bone and accelerated bone resorption, especially in rheumatoid arthritis patients with inflammatory conditions. Pilose antler peptide (PAP) isolated and purified from deer antlers has been shown to have beneficial effects on chronic inflammation. In the present study, we studied the impact of PAP on osteoblast differentiation and evaluated the regulatory mechanism, with particular emphasis on the effect of PAP on TNF-α-mediated NF-κB signaling. Mouse primary osteoblast cells were activated with bone morphogenetic protein-2 (BMP-2) for osteoblast differentiation. A significant stimulatory effect of PAP in osteoblastogenesis was observed using ALP activity and Alizarin Red S staining assays. Meanwhile, PAP significantly rescued TNF-α-induced impairment of osteoblast formation as well as mineralization. Furthermore, we found a similar trend upon analyzing osteoblast-specific gene expression. PAP significantly rescued TNF-α-mediated decrease in expression of osteoblast-specific genes. A molecular mechanism assay indicated that PAP significantly inhibited TNF-α-mediated stimulation of NF-κB signaling activity, as well as nuclear translocation of its subunit p65. Moreover, over-expression of p65 reversed the stimulatory effects of PAP on osteoblast differentiation. Furthermore, we also identified that PAP dose dependently inhibit osteoclastogenesis, and this effect might be achieved via suppressing NF-κB activity. In summary, this study shows that PAP promotes osteoblast differentiation and blocks TNF-α-mediated suppression of osteoblastogenesis in vitro via the NF-κB/p65 pathway, as well as inhibits osteoclastsogenesis in vitro. Therefore, PAP, a novel drug with both antiresorptive and osteoanabolic activity, shows therapeutic potential as an alternative treatment for osteolytic diseases, including rheumatoid arthritis and osteoporosis. - Highlights: • PAP promotes osteoblasts differentiation and inhibits osteoclastogenesis. • PAP blocks TNFα-mediated suppression of osteoblastogenesis via NF-κB pathway. • PAP shows both antiresorptive and osteoanabolic activity, and is promising in the treatment of inflammatory bone loss.},
doi = {10.1016/J.BBRC.2017.07.091},
journal = {Biochemical and Biophysical Research Communications},
issn = {0006-291X},
number = 2,
volume = 491,
place = {United States},
year = {2017},
month = {9}
}