Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
CONTINUING EDUCATION The biology of orthodontic tooth movement part 2: modulating tooth movement via nitric oxide and prostaglandin production Dr. Michael S. Stosich reviews the markers of bone cell activity that are intrinsic to the complex process of bone modeling and remodeling Modulation of bone for orthodontic tooth Movement In the ever complex process of bone modeling and remodeling, certain markers of bone cell activity have been shown to act as key players that in part govern the process. Nitric oxide (NO) and prostaglandin (PGE2) production have been used as parameters in bone cell mechanosensitivity in the study of bone remodeling. Turner, et al.,1 have shown that NO and PGE2 act as mediators in the bone formation process in vivo. Loading bone cells mechanically is also associated with an increased production of PGE2.2 When nitric oxide synthase (iNOS) is inhibited, the loading response in bone ceases.3 This indicates the essential role of NO in the early stages of bone remodeling. The production of NO and PGE2 by primary bone cells is dependent upon applied stress. Bone cells might detect mechanical signals through fluid flow, and mechanical loading of bone causes flow of interstitial fluid through the canalicular network.4 Using cyclic strains, PGE2 nor NO could be detected; however, under low levels of fluid flow, rapid production of both agents was induced.4 Bone cells treated Michael S. Stosich, DMD, MS, MS, has performed orthodontic and craniofacial reconstruction work throughout the world, but his first priority is his patients at iDentity Orthodontics in the Chicagoland area. With educational credentials and training twice that required of an orthodontist, Dr. Stosich has published and lectured throughout the United States and abroad. His sincere interest and dedication toward the study of stem cell tissue engineering, combined with a rare creativity toward scientific discovery, paved the way for Dr. Stosich to serve as lead scientist in a variety of studies. This yielded numerous publications that lead to important advancements in craniofacial cases. His achievements were also awarded by the National Institutes of Health, which endowed grants toward future study. Dr. Stosich is also faculty at the University of Chicago Medicine. Dr. Stosich believes in giving back to the communities he serves and focuses on charitable giving where it can do the most good by treating underserved and unprivileged children through his involvement in the Smiles Change Lives foundation, Smiles for Service, and his work on the Chicago craniofacial team. Dr. Stosich is also involved in local community programs linking orthodontics to philanthropy. [email protected] xx Orthodontic practice Educational aims and objectives This article aims to identify markers of bone cell activity that have been shown to act as key players in the process of bone modeling and remodeling. Expected outcomes Correctly answering the questions on page XX, worth 2 hours of CE, will demonstrate the reader can: • Identify the roles that nitric oxide (NO) and prostaglandin (PGE2) production play in the process. • Realize the therapeutic range of ultrasound in stimulation of bone formation and osteoblast proliferation. with pulsating fluid flow (PFF) of increasing flow rate rapidly stimulate the production of NO in a manner that is dose dependent5. PGE2 production tended to be higher as a result of increased shear stress on the cells, which was achieved by increasing the flow rate.5 These results offer sound evidence for the importance of shear stress as a stimulus on bone cell walls in the process of bone cell mechanotransduction remodeling. Ultrasound stimulates NO and PGE2 production of human osteoblasts Reher, et al.,6 have shown that in bone repair both osteogenesis and angiogenesis are essential, and it has been shown that the therapeutic range of ultrasound stimulates bone formation and osteoblast proliferation, and stimulates the synthesis of angiogenic factors, endothelial growth factors, basic fibroblast growth factors, and interleukin-8. The ultrasound may in fact act like mechanical stress on the bone and stimulate PGE2 and NO production, which are essential for bone remodeling. NO production in bone showed a marked increase when treated with 45 kHz of therapeutic ultrasound. Furthermore, iNOS and L-NAA had an inhibitory effect on the ultrasound therapy. Similarly, higher levels of PGE2 were detected when the bone was subjected to ultrasound, and COX-2 inhibited PGE2 synthesis at a frequency of 45 kHz. These results show that when bone is subjected to a therapeutic range of ultrasound, osteoblasts are stimulated to produce NO and PGE2. The synthesis of PGE2 appears to be promoted by the inducible cycloxygenase pathway (COX-2). It may also be inferred that L-arginine is crucial in the NO pathway. It has been shown that NO and PGE2 are essential in the bone remodeling process. The studies here support the idea that varying forms of mechanical therapy, be it from shear stress or ultrasound, elucidate a prominent increase in NO and PGE2 activity, which may in turn lead to new possibilities for increasing turnover time in bone remodeling, and potentially more rapid orthodontic tooth movement. OP References 1. Turner CH, Owan I, Jacob DS, McClintock R, Peacock M. Effects of nitric oxide synthase inhibitors on bone formation in rats. Bone. 1997;21(6):487-490. 2. Binderman I, Zor U, Kaye AM, Shimshoni Z, Harell A, Sömjen. The transduction of mechanical force into biochemical events in bone cells may involve activation of phospholipase A2. Calcif Tissue Int. 1988;42(4):261-266. 3. Fox SW, Chambers TJ, Chow, JW. Nitric oxide as an early mediator of the increase in bone formation by mechanical stimulation. Am J Physiol. 1996;270(6 Pt 1):E955-E960. 4. Smalt R, Mitchell FT, Howard RL, Chambers TJ. Mechanotransduction in bone cells: induction of nitric oxide and prostaglandin synthesis by fluid shear stress, but not by mechanical strain. Adv Exp Med Biol. 1997;433:311-314. 5. Bakker AD, Soejima K, Klein-Nulend J, Burger EH. The production of nitric oxide and prostaglandin E(2) by primary bone cells is shear stress dependent. J Biomech.2001;34(5):671-677. 6. Reher P, Harris M, Whiteman M, Hai HK, Meghji S. Ultrasound stimulates nitric oxide and prostaglandin E2 production by human osteoblasts. Bone. 2002;31(1):236241. Volume 5 Number 1