title: Poly(ADP-ribose) in the bone: from oxidative stress signal to structural element.
abstract: Contrary to common perception bone is a dynamic organ flexibly adapting to changes in mechanical loading by shifting the delicate balance between bone formation and bone resorption carried out by osteoblasts and osteoclasts, respectively. In the past decades numerous studies demonstrating production of reactive oxygen or nitrogen intermediates, effects of different antioxidants, and involvement of prototypical redox control mechanisms (Nrf2-Keap1, Steap4, FoxO, PAMM, caspase-2) have proven the central role of redox regulation in the bone. Poly(ADP-ribosyl)ation (PARylation), a NAD-dependent protein modification carried out by poly(ADP-ribose) polymerase (PARP) enzymes recently emerged as a new regulatory mechanism fine-tuning osteoblast differentiation and mineralization. Interestingly PARylation does not simply serve as a signaling mechanism during osteoblast differentiation but also couples it to osteoblast death. Even more strikingly, the poly(ADP-ribose) polymer likely released from succumbed cells at the terminal stage of differentiation is incorporated into the bone matrix representing the first structural role of this versatile biopolymer. Moreover, this new paradigm explains why and how osteodifferentiation and death of cells entering this pathway are closely coupled to each other. Here we review the role of reactive oxygen and nitrogen intermediates as well as PARylation in osteoblast and osteoclast differentiation, function, and cell death.
authors: Department of Medical Chemistry, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
authors: Csaba
authors: C
authors: Hegedűs
authors: Department of Medical Chemistry, Faculty of Medicine, University of Debrecen, Debrecen, Hungary; Department of Environmental Pollution Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, Poland.
authors: Agnieszka
authors: A
authors: Robaszkiewicz
authors: Department of Medical Chemistry, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
authors: Petra
authors: P
authors: Lakatos
authors: Division of Dermatology, Faculty of Medicine, University of Debrecen, Nagyerdei krt 98, H-4032 Debrecen, Hungary. Electronic address: eszabo@med.unideb.hu.
authors: Éva
authors: É
authors: Szabó
authors: Department of Medical Chemistry, Faculty of Medicine, University of Debrecen, Debrecen, Hungary; MTA-DE Cell Biology and Signaling Research Group, Debrecen, Hungary. Electronic address: lvirag@med.unideb.hu.
authors: László
authors: L
authors: Virág
mesh_terms: D000975:Antioxidants / Q000378:metabolism; D001842:Bone and Bones / Q000378:metabolism; D002454:Cell Differentiation; D006801:Humans; D010006:Osteoblasts / Q000166:cytology* / Q000378:metabolism; D010010:Osteoclasts / Q000166:cytology* / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology; D011064:Poly Adenosine Diphosphate Ribose / Q000378:metabolism*; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D026361:Reactive Nitrogen Species / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D000975:Antioxidants; D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species; D011064:Poly Adenosine Diphosphate Ribose; D011065:Poly(ADP-ribose) Polymerases
keywords: Osteoblast; Osteoclast; Poly(ADP-ribose); Poly(ADP-ribose) glycohydrolase; Poly(ADP-ribose) polymerase; Reactive nitrogen intermediates; Reactive oxygen intermediates