Chao Xu1, Su Ni2, Chao Zhuang3, Chenkai Li2, Gongyin Zhao3, Shijie Jiang3, Liangliang Wang3, Ruixia Zhu3, Andre J van Wijnen4, Yuji Wang5,6,7. 1. Trauma Center, The Affiliated Changzhou No.2 People's Hospital of Nanjing Medical University, 29 Xinglong Alley, Changzhou, 213003, China. 2. Medical Research Center, The Affiliated Changzhou No.2 People's Hospital of Nanjing Medical University, 29 Xinglong Alley, Changzhou, 213003, China. 3. Department of Orthopedics, The Affiliated Changzhou No.2 People's Hospital of Nanjing Medical University, 29 Xinglong Alley, Changzhou, 213003, China. 4. Department of Orthopedic Surgery and Biochemistry & Molecular Biology, Mayo Clinic, Rochester, MN, USA. vanwijnen.andre@mayo.edu. 5. Department of Orthopedics, The Affiliated Changzhou No.2 People's Hospital of Nanjing Medical University, 29 Xinglong Alley, Changzhou, 213003, China. yujiwang@sohu.com. 6. Department of Orthopedic Surgery and Biochemistry & Molecular Biology, Mayo Clinic, Rochester, MN, USA. yujiwang@sohu.com. 7. Department of Orthopedics, The Third Affiliated Hospital of Gansu University of Chinese Medicine, 222 Silong Road, Baiyin, 730900, China. yujiwang@sohu.com.
Abstract
OBJECTIVE: Chondrocyte apoptosis plays a vital role in osteoarthritis (OA) progression. Angelica sinensis polysaccharide (ASP), a traditional Chinese medicine, possesses anti-inflammatory and anti-apoptotic properties in chondrocytes. This study aimed to determine the protective role of ASP on sodium nitroprusside (SNP)-induced chondrocyte apoptosis, and explore the underlying mechanism. METHOD: Human primary chondrocytes isolated from the articular cartilage of OA patients were treated with SNP alone or in combination with different doses of ASP. Cell viability and apoptosis were assessed, and apoptosis-related proteins including Bcl-2 and Bax were detected. Autophagy levels were evaluated by light chain 3 (LC3) II immunofluorescence staining, mRFP-GFP-LC3 fluorescence localization, and western blot (LC3II, p62, Beclin-1, Atg5). Meanwhile, activation of the ERK 1/2 pathway was determined by western blot. The autophagy inhibitors, 3-methyladenine (3-MA), chloroquine (CQ), and a specific inhibitor of ERK1/2, SCH772984, were used to confirm the autophagic effect of ASP. RESULTS: The results showed that SNP-induced chondrocyte apoptosis was significantly rescued by ASP, whereas ASP alone promoted chondrocyte proliferation. The anti-apoptotic effect of ASP was related to the enhanced autophagy and depended on the activation of the ERK1/2 pathway. CONCLUSION: ASP markedly rescued SNP-induced apoptosis by activating ERK1/2-dependent autophagy in chondrocytes, and it made ASP as a potential therapeutic supplementation for OA treatment.
OBJECTIVE: Chondrocyte apoptosis plays a vital role in osteoarthritis (OA) progression. Angelica sinensispolysaccharide (ASP), a traditional Chinese medicine, possesses anti-inflammatory and anti-apoptotic properties in chondrocytes. This study aimed to determine the protective role of ASP on sodium nitroprusside (SNP)-induced chondrocyte apoptosis, and explore the underlying mechanism. METHOD:Human primary chondrocytes isolated from the articular cartilage of OA patients were treated with SNP alone or in combination with different doses of ASP. Cell viability and apoptosis were assessed, and apoptosis-related proteins including Bcl-2 and Bax were detected. Autophagy levels were evaluated by light chain 3 (LC3) II immunofluorescence staining, mRFP-GFP-LC3 fluorescence localization, and western blot (LC3II, p62, Beclin-1, Atg5). Meanwhile, activation of the ERK 1/2 pathway was determined by western blot. The autophagy inhibitors, 3-methyladenine (3-MA), chloroquine (CQ), and a specific inhibitor of ERK1/2, SCH772984, were used to confirm the autophagic effect of ASP. RESULTS: The results showed that SNP-induced chondrocyte apoptosis was significantly rescued by ASP, whereas ASP alone promoted chondrocyte proliferation. The anti-apoptotic effect of ASP was related to the enhanced autophagy and depended on the activation of the ERK1/2 pathway. CONCLUSION:ASP markedly rescued SNP-induced apoptosis by activating ERK1/2-dependent autophagy in chondrocytes, and it made ASP as a potential therapeutic supplementation for OA treatment.
Authors: E Maneiro; M J López-Armada; M C de Andres; B Caramés; M A Martín; A Bonilla; P Del Hoyo; F Galdo; J Arenas; F J Blanco Journal: Ann Rheum Dis Date: 2005-03 Impact factor: 19.103
Authors: Giuseppe Musumeci; Paola Castrogiovanni; Francesca Maria Trovato; Annelie Martina Weinberg; Mohammad K Al-Wasiyah; Mohammed H Alqahtani; Ali Mobasheri Journal: Int J Mol Sci Date: 2015-08-31 Impact factor: 5.923