Published 6 issues per year
ISSN Print: 1045-4403
ISSN Online: 2162-6502
Indexed in
Role of Apoptosis in Glucocorticoid-Induced Osteoporosis and Osteonecrosis
ABSTRACT
Bone disease is a side effect of concern regarding chronic glucocorticoid (GC) administration. Most GC-treated patients exhibit a process of bone loss, frequently leading to osteoporosis, with increased fracture risk, especially in spinal vertebrae. Some GC-treated patients will develop osteonecrosis, a disease with distinct clinical and histopathological features, most often occurring underneath the articular surface of the femoral head. Remarkably, both of these GC-induced bone diseases are associated with osteoblast and osteocyte apoptosis, which is emerging as a potential primary pathogenic mechanism. Here, we review the evidence for osteoblast and osteocyte apoptosis in GC-induced bone disease and highlight current debates: (1) With recent reports describing the antiapoptotic effect of GCs in some in vitro osteoblast models, and with the known adverse effects of GCs on osteoblast cell cycle and differentiation, could the in vivo osteoblast apoptosis be an indirect rather than a direct effect of GCs? (2) What is the pathogenic relationship between GC-induced osteoporosis and osteonecrosis? Could the latter be a mere manifestation of the former? and (3) How does apoptosis fit into the traditional concept of ischemia as a key etiology in osteonecrosis? Regardless of the answers, recent studies with cells, animals, and humans point out bone cell apoptosis as a potential target in the design of treatment for GC-induced bone disease.
-
Leclerc Nathalie, Noh Tommy, Cogan Jon, Samarawickrama Dilan B., Smith Elisheva, Frenkel Baruch, Opposing effects of glucocorticoids and Wnt signaling on Krox20 and mineral deposition in osteoblast cultures, Journal of Cellular Biochemistry, 103, 6, 2008. Crossref
-
Espina B., Liang M., Russell R.G.G., Hulley P.A., Regulation of bim in glucocorticoid-mediated osteoblast apoptosis, Journal of Cellular Physiology, 215, 2, 2008. Crossref
-
Qin Weiping, Bauman William A., Cardozo Christopher, Bone and muscle loss after spinal cord injury: organ interactions, Annals of the New York Academy of Sciences, 1211, 1, 2010. Crossref
-
Bodine Peter V.N., Billiard Julia, Moran Robert A., Ponce-de-Leon Helga, McLarney Sean, Mangine Annamarie, Scrimo Melissa J., Bhat Ramesh A., Stauffer Barbara, Green Jack, Stein Gary S., Lian Jane B., Komm Barry S., The Wnt antagonist secreted frizzled-related protein-1 controls osteoblast and osteocyte apoptosis, Journal of Cellular Biochemistry, 96, 6, 2005. Crossref
-
Hadjigeorgiou Georgios M., Malizos Konstantinos, Dardiotis Efthimios, Aggelakis Konstantinos, Dardioti Maria, Zibis Aristidis, Dimitroulias Apostolos, Scarmeas Nikolaos, Tsezou Aspasia, Karantanas Apostolos, Paraoxonase 1 gene polymorphisms in patients with osteonecrosis of the femoral head with and without cerebral white matter lesions, Journal of Orthopaedic Research, 25, 8, 2007. Crossref
-
Spreafico Adriano, Frediani Bruno, Capperucci Caterina, Leonini Alessandra, Gambera Dario, Ferrata Paolo, Rosini Sergio, Di Stefano Anna, Galeazzi Mauro, Marcolongo Roberto, Osteogenic growth peptide effects on primary human osteoblast cultures: Potential relevance for the treatment of glucocorticoid-induced osteoporosis, Journal of Cellular Biochemistry, 98, 4, 2006. Crossref
-
Leclerc Nathalie, Noh Tommy, Khokhar Arvinder, Smith Elisheva, Frenkel Baruch, Glucocorticoids inhibit osteocalcin transcription in osteoblasts by suppressing Egr2/Krox20-binding enhancer, Arthritis & Rheumatism, 52, 3, 2005. Crossref
-
McNeer Jennifer L., Nachman James B., The optimal use of steroids in paediatric acute lymphoblastic leukaemia: no easy answers, British Journal of Haematology, 149, 5, 2010. Crossref
-
Abu-Id M. H., Açil Y., Gottschalk J., Kreusch T., Bisphosphonatassoziierte Osteonekrose des Kiefers, Mund-, Kiefer- und Gesichtschirurgie, 10, 2, 2006. Crossref
-
Fatokun Amos A., Stone Trevor W., Smith Robert A., Responses of differentiated MC3T3-E1 osteoblast-like cells to reactive oxygen species, European Journal of Pharmacology, 587, 1-3, 2008. Crossref
-
ABU-ID Mario H., WARNKE Patrick H., GOTTSCHALK Joachim, SPRINGER Ingo, WILTFANG Jörg, ACIL Yahya, RUSSO Paul A.J., KREUSCH Thomas, “Bis-phossy jaws” – High and low risk factors for bisphosphonate-induced osteonecrosis of the jaw, Journal of Cranio-Maxillofacial Surgery, 36, 2, 2008. Crossref
-
Korcok Jasminka, Jeffrey Dixon S, Sims Stephen, P2 Nucleotide Receptor Signaling in Osteoclasts, in Nucleotides and Regulation of Bone Cell Function, 2006. Crossref
-
Chaves Neto Antonio Hernandes, Machado Daisy, Yano Cláudia Lumy, Ferreira Carmen Veríssima, Antioxidant defense and apoptotic effectors in ascorbic acid and β-glycerophosphate-induced osteoblastic differentiation, Development, Growth & Differentiation, 53, 1, 2011. Crossref
-
Ko Jih-Yang, Wang Feng-Sheng, Wang Ching-Jen, Wong To, Chou Wen-Yi, Tseng Shin-Ling, Increased Dickkopf-1 expression accelerates bone cell apoptosis in femoral head osteonecrosis, Bone, 46, 3, 2010. Crossref
-
Xing Lianping, Boyce Brendan F., Regulation of apoptosis in osteoclasts and osteoblastic cells, Biochemical and Biophysical Research Communications, 328, 3, 2005. Crossref
-
Lemaire Irma, Di Virgilio Francesco, Purinergic Signaling in Inflammation and Immunomodulation, in Nucleotides and Regulation of Bone Cell Function, 2006. Crossref
-
Adinolfi Elena, Amoroso Francesca, Giuliani Anna Lisa, P2X7 Receptor Function in Bone-Related Cancer, Journal of Osteoporosis, 2012, 2012. Crossref
-
Bauman William A., Schnitzer Thomas J., Chen David, Management of Osteoporosis After Spinal Cord Injury: What Can Be Done?, PM&R, 2, 6, 2010. Crossref
-
Inkielewicz-Stepniak Iwona, Radomski Marek W., Wozniak Michal, Fisetin prevents fluoride- and dexamethasone-induced oxidative damage in osteoblast and hippocampal cells, Food and Chemical Toxicology, 50, 3-4, 2012. Crossref
-
Baroja-Mazo Alberto, Pelegrín Pablo, Modulating P2X7 Receptor Signaling during Rheumatoid Arthritis: New Therapeutic Approaches for Bisphosphonates, Journal of Osteoporosis, 2012, 2012. Crossref
-
Burnstock Geoffrey, Arnett Timothy R., Orriss Isabel R., Purinergic signalling in the musculoskeletal system, Purinergic Signalling, 9, 4, 2013. Crossref
-
Kvist Torben Madsen, Schwarz Peter, Jørgensen Niklas Rye, The P2X7 Receptor: A Key Player in Immune-Mediated Bone Loss?, The Scientific World Journal, 2014, 2014. Crossref
-
Kim Jinhee, Lee Hyejin, Kang Ki Sung, Chun Kwang-Hoon, Hwang Gwi Seo, Protective effect of Korean Red Ginseng against glucocorticoid-induced osteoporosis in vitro and in vivo, Journal of Ginseng Research, 39, 1, 2015. Crossref
-
BONEWALD LYNDA F., Osteocytes, in Osteoporosis, 2008. Crossref
-
Zhang Xiaojun, Zhang Jianbao, Qu Xuemin, Wen Jun, Effects of Different Extremely Low-Frequency Electromagnetic Fields on Osteoblasts, Electromagnetic Biology and Medicine, 26, 3, 2007. Crossref
-
Le Ha Thi -Ngan, Phi Lan Thi, Dao Thuy Thi-Thanh, Phan Ngoc Kim, Van Pham Phuc, Vu Ngoc Bich, A mouse model of osteonecrotic femoral head induced by methylprednisolone and liposaccharide, Biomedical Research and Therapy, 3, 3, 2016. Crossref
-
CHEN SEN, LI JIANPING, PENG HAO, ZHOU JIANLIN, FANG HONGSONG, Administration of erythropoietin exerts protective effects against glucocorticoid-induced osteonecrosis of the femoral head in rats, International Journal of Molecular Medicine, 33, 4, 2014. Crossref
-
Plesa Maria, Gagné Vincent, Glisovic Sanja, Younan Melissa, Sharif-Askari Bahram, Laverdière Caroline, Alos Nathalie, Leclerc Jean-Marie, Sallan Stephen E, Neuberg Donna, Kutok Jeffery L, Silverman Lewis B, Sinnett Daniel, Krajinovic Maja, Influence of BCL2L11 polymorphism on osteonecrosis during treatment of childhood acute lymphoblastic leukemia, The Pharmacogenomics Journal, 19, 1, 2019. Crossref
-
Ersoy Alpaslan, Kahvecioglu Serdar, Ersoy Canan, Akdag Ibrahim, Yurtsever Ismail, Dilek Kamil, Is glucocorticoid-induced osteonecrosis after kidney transplantation related to osteoporosis?, Nephrology Dialysis Transplantation, 21, 5, 2006. Crossref
-
Zhang Qiankun, L v Jin, Jin Lie, Role of coagulopathy in glucocorticoid-induced osteonecrosis of the femoral head, Journal of International Medical Research, 46, 6, 2018. Crossref
-
GAO YOU-SHUI, GUO SHANG-CHUN, DING HAO, ZHANG CHANG-QING, Caspase-3 may be employed as an early predictor for fracture-induced osteonecrosis of the femoral head in a canine model, Molecular Medicine Reports, 6, 3, 2012. Crossref
-
Huang Gangyong, Wei Yibing, Zhao Guanglei, Xia Jun, Wang Siqun, Wu Jianguo, Chen Feiyan, Chen Jie, Shi Jingshen, Microarray-based screening of differentially expressed genes in glucocorticoid-induced avascular necrosis, Molecular Medicine Reports, 15, 6, 2017. Crossref
-
Ceponis P, Keilman C, Guerry C, Freiberger JJ, Hyperbaric oxygen therapy and osteonecrosis, Oral Diseases, 23, 2, 2017. Crossref
-
Jia Yan-Bo, Jiang Dian-Ming, Ren Yi-Zhong, Liang Zi-Hong, Zhao Zhen-Qun, Wang Yu-Xin, Inhibitory effects of vitamin E on osteocyte apoptosis and DNA oxidative damage in bone marrow hemopoietic cells at early stage of steroid-induced femoral head necrosis, Molecular Medicine Reports, 15, 4, 2017. Crossref
-
Tomori Yuji, Motoda Norio, Ohashi Ryuji, Sawaizumi Takuya, Nanno Mitsuhiko, Takai Shinro, Preiser disease after repeated local glucocorticoid injections, Medicine, 97, 38, 2018. Crossref
-
Cui Daping, Zhao Dewei, Wang Benjie, Liu Baoyi, Yang Lei, Xie Hui, Wang Zihua, Cheng Liangliang, Qiu Xing, Ma Zhijie, Yu Mingyang, Wu Di, Long Hao, Safflower (Carthamus tinctorius L.) polysaccharide attenuates cellular apoptosis in steroid-induced avascular necrosis of femoral head by targeting caspase-3-dependent signaling pathway, International Journal of Biological Macromolecules, 116, 2018. Crossref
-
Deng Shuang, Dai Guo, Chen Sen, Nie Zhigang, Zhou Jianlin, Fang Hongsong, Peng Hao, Dexamethasone induces osteoblast apoptosis through ROS-PI3K/AKT/GSK3β signaling pathway, Biomedicine & Pharmacotherapy, 110, 2019. Crossref
-
Horsch Kay, de Wet Heidi, Schuurmans Macé M., Allie-Reid Fatima, Cato Andrew C. B., Cunningham John, Burrin Jacky M., Hough F. Stephen, Hulley Philippa A., Mitogen-Activated Protein Kinase Phosphatase 1/Dual Specificity Phosphatase 1 Mediates Glucocorticoid Inhibition of Osteoblast Proliferation, Molecular Endocrinology, 21, 12, 2007. Crossref
-
Xie Hui, Tang Ling-Li, Luo Xiang-Hang, Wu Xi-Yu, Wu Xian-Ping, Zhou Hou-De, Yuan Ling-Qing, Liao Er-Yuan, Suppressive effect of dexamethasone on TIMP-1 production involves murine osteoblastic MC3T3-E1 cell apoptosis, Amino Acids, 38, 4, 2010. Crossref
-
Brant Jeannine M., Viale Pamela Hallquist, Lin Albert, Exposed Bone in Oral Cavities, Clinical Journal of Oncology Nursing, 9, 3, 2005. Crossref
-
Frenkel Baruch, White Wendy, Tuckermann Jan, Glucocorticoid-Induced Osteoporosis, in Glucocorticoid Signaling, 872, 2015. Crossref
-
Lemaire Irma, Falzoni Simonetta, Leduc Natacha, Zhang Bin, Pellegatti Patrizia, Adinolfi Elena, Chiozzi Paola, Di Virgilio Francesco, Involvement of the Purinergic P2X7Receptor in the Formation of Multinucleated Giant Cells, The Journal of Immunology, 177, 10, 2006. Crossref
-
Zhan Jingdi, Yan Zijian, Zhao Mengyao, Qi Weihui, Lin Jian, Lin Zeng, Huang Yijiang, Pan Xiaoyun, Xue Xinghe, Allicin inhibits osteoblast apoptosis and steroid-induced necrosis of femoral head progression by activating the PI3K/AKT pathway, Food & Function, 11, 9, 2020. Crossref
-
Nie Zhigang , Deng Shuang , Zhang Lei , Chen Sen , Lu Qiang , Peng Hao , Crocin protects against dexamethasone‑induced osteoblast apoptosis by inhibiting the ROS/Ca2+‑mediated mitochondrial pathway, Molecular Medicine Reports, 2019. Crossref
-
Wang Feng-Sheng, Ko Jih-Yang, Yeh Da-Wei, Ke Huei-Ching, Wu Hsing-Long, Modulation of Dickkopf-1 Attenuates Glucocorticoid Induction of Osteoblast Apoptosis, Adipocytic Differentiation, and Bone Mass Loss, Endocrinology, 149, 4, 2008. Crossref
-
Zhao Jun, Mu Long, Wang Zhengchun, Fang Xiangchun, He Xuefeng, Zhang Xiaofeng, Xu Xilin, The potential roles of circular RNAs in osteonecrosis of the femoral head (Review), Molecular Medicine Reports, 2019. Crossref
-
Fan Zhen‐Qi, Bai Shu‐Cai, Xu Qian, Li Zhi‐Jun, Cui Wen‐Hao, Li Hui, Li Xiao‐Hui, Zhang Hua‐Feng, Oxidative Stress Induced Osteocyte Apoptosis in Steroid‐Induced Femoral Head Necrosis, Orthopaedic Surgery, 13, 7, 2021. Crossref
-
Jing Xingzhi, Du Ting, Yang Xiaoxia, Zhang Weimin, Wang Guodong, Liu Xiaoyang, Li Tao, Jiang Zhensong, Desferoxamine protects against glucocorticoid‐induced osteonecrosis of the femoral head via activating HIF‐1α expression, Journal of Cellular Physiology, 235, 12, 2020. Crossref
-
Nie Zhigang, Chen Sen, Deng Shuang, Long Linsheng, Peng Puji, Gao Mingyong, Cheng Shile, Cao Jiarui, Peng Hao, Gene expression profiling of osteoblasts subjected to dexamethasone-induced apoptosis with/without GSK3β-shRNA, Biochemical and Biophysical Research Communications, 506, 1, 2018. Crossref
-
Jiang Chaolai, Zhou Zubin, Lin Yiwei, Shan Haojie, Xia Wenyang, Yin Fuli, Wang Nan, Zhou Lihui, Gao Youshui, Yu Xiaowei, Astragaloside IV ameliorates steroid-induced osteonecrosis of the femoral head by repolarizing the phenotype of pro-inflammatory macrophages, International Immunopharmacology, 93, 2021. Crossref
-
Zhao Xiaodong, Yang Fuqiang, Sun Luwei, Zhang Ali, Association between NOS3 polymorphisms and osteonecrosis of the femoral head, Artificial Cells, Nanomedicine, and Biotechnology, 47, 1, 2019. Crossref