CHEMICAL MEDIATORS INFLUENCING ORHODONTIC TOOTH MOVEMENT INDIAN DENTAL ACADEMY Leader in continuing dental education www.indiandentalacademy.com
OVER VIEW •Tooth structure (pdl) •Sensors in tooth structure. •Physiologic tooth movement •Orthodontic tooth movement www.indiandentalacademy.com
•Precondition for tooth movement •Factors influencing •In which tooth movement these mediators are found •Drug interaction with chemical mediators www.indiandentalacademy.com
Tooth structure: • each tooth is attached to and seperated from the adjacent alveolar bone by a heavy collagenous supporting structure. • Width – approximately 0.5mm around all parts of roots www.indiandentalacademy.com
â€˘ The major component of the ligament is a network of parallel collagenous fibers inserting into cementum of the root on one side and dense bony plate , lamina dura on other side.
â€˘ These supporting fibers run at an angle attaching farther apically on the tooth than on the adjacent alveolar bone. â€˘ This arrangement resists the displacement of the tooth expected during normal function. www.indiandentalacademy.com
The other major constituents of the periodontal ligament are â€˘ The cellular elements, including mesenchymal cells of various types along with vascular and neural elements â€˘ The tissue fluids. www.indiandentalacademy.com
â€˘ Both play an important role in normal function and in making orthodontic tooth movement possible. â€˘ Principle changes in periodontal ligament are â€“ undifferentiated mesenchymal cells & their progeny in the form of fibroblasts and osteoblasts www.indiandentalacademy.com
â€˘ Undifferentiated mesenchymal cells under tension differentiate into osteoclasts & cementoclasts, these same cells under pressure differentiate into osteoblasts, fibroblasts and cementoblasts. â€˘ Periodontal ligament is not highly vascular, but it does contain blood vessels and cells from the vascular system. www.indiandentalacademy.com
a z n a r a k â€˘ Nerve endings are also found with in the ligament, both the unmyelinated free endings associated with perception of pain & the more complex receptors associated with pressure & positional information(proprioception) â€˘ Nerve bundles pass into the periodontal ligament from the periapical area & through channels from the alveolar bone that follow the course of the blood vessels www.indiandentalacademy.com
• They divide into single myelinated fibers, which ultimately lose their myelin sheaths & end in one of four types of neural termination. • Free endings which have a tree like configuration & carry pain sensation. • Ruffini – like mechanoreceptors , located primarily in the apical area. www.indiandentalacademy.com
• Coiled Meissner’s corpuscles , also mechanoreceptors, found mainly in the mid root region. • Spindle like pressure & vibration endings which are surrounded by a fibrous capsule & located mainly in the apex www.indiandentalacademy.com
â€˘ PDL space is fluid filled. This fluid is derived from the vascular system. â€˘ A fluid filled chamber with retentive but porous walls could be a description of shock absorber & in normal function , the fluid allows the PDL space to play this role. www.indiandentalacademy.com
Physiologic tooth movement: â€˘ if an object is subjected to set of forces but remains in the same position, those forces must be in balance or in equilibrium. â€˘ Teeth normally experience forces from masticatory effort, swallowing & speaking but do not move. www.indiandentalacademy.com
â€˘ If a tooth is subjected to a continuous force from the orthodontic appliance, it does move. â€˘ The force applied by the orthodontist has altered the previous equilibrium , resulting in tooth movement. www.indiandentalacademy.com
â€˘ One of the factors which contribute to the dental equilibrium is the periodontal fiber system. â€˘ If a tooth is lost, the space tends to close, in part because of the forces created by the transseptal fibers in the gingiva. â€˘ This was demonstrated experimentally on monkeys. www.indiandentalacademy.com
â€˘ PL also influences eruption of teeth. Eruption mechanism remains potentially active through out life. â€˘ Since a tooth can begin to erupt again many years after eruptive movements are apparently ceased, if its antagonist is extracted. www.indiandentalacademy.com
Orthodontic tooth movement â€˘ Orthodontic tooth movement is induced by mechanical stimuli and facilitated by remodeling of the periodontal ligament & alveolar bone.
Bone â€˘ Bone is of 2 types 1. Cortical 2. & Cancellous .
Cortical bone • Cortical bone looks dense & compact & constitutes 80% of the skeleton forming the inner &outer layers of tubular appearing appendicular bone,inner & outer tables of flat bones & inner & outer surfaces of vertebral bodies. • Cortical bone is engineered to protect vital organs.it consists of haversian systems with 4 – 20 circumferential rings of concentrically arranged lamellae that encompasses a central canal. • Haversian systems in cortical bone function as buttresses. www.indiandentalacademy.com
Cancellous bone • Interposed between cortical bone is the spongy looking cancellous bone. • A 3 dimensional lattice of trabeculae is the hall mark of this struicture. • Spatial orientation of trabeculae is random. • Rather than being engineered for loading cancellous bone has been designed to respond rapidly to physiologic requirements. www.indiandentalacademy.com
Bone consists of 4 microstructural components
1. Cells –
•Osteoblasts •Osteocytes •osteoclasts
2. Organic matrix 3. Inorganic matrix 4. Soluble signalling factors www.indiandentalacademy.com
â€˘ All cells are derived from mesenchymal cell lineage. â€˘ Undifferentiated mesenchymal stem cells Determined osteoprogenitor cells
Inducible osteoprogenitor cells
For bone formation For fracture repair www.indiandentalacademy.com during embryogenesis
â€˘ According to Brighton following fracture with in 12 hrs polymorphic mesenchymal cells appear providing preosteoblastic cell resource. â€˘ Depending on the presence of environmental cues such as nutrient supply, specific growth factors, blood vessels & mechanical stability , they can convert either to cartilage forming chondrocytes or bone forming osteoblasts. www.indiandentalacademy.com
Osteoblasts • Osteoblasts are metabolically active secretory cells that express soluble signaling factors ex: BMP’s, TGF- beta, insulin like growth factor I & II , interleukin – 1 & platelet derived growth factor & osteoid. • Expression of these factors by osteoblasts occurs during bone embryogenesis, maintenance(ex: remodeling) & repair. www.indiandentalacademy.com
â€˘ During remodeling , osteoid is produced at the rate of 2 - 3 micrometers per day at a thickness of 20 micrometers. â€˘ After a maturational period of 10 days, osteoid mineralises at a rate of 1- 2 micro meters per day.
Osteocytes â€˘ These are relatively inactive cells. Their subdued metabolic activity is crucial to bone viability & to sustain homeostasis. â€˘ The complex processes of homeostasis are regulated by physiologic interactions among cells, tissues, organs & signaling factors such as harmones & growth factors that meticulously titrate intra & extra cellular levels of cationic & anionic moieties www.indiandentalacademy.com
â€˘ Vitality of bone is maintained through a network of osteocytic cytoplasmic processes that traverse canaliculi. â€˘ This highway system enables osteocytes to interact through gap junctions & permits signal transmission to osteoblasts from osteocytes & from osteocytes to osteoblasts. www.indiandentalacademy.com
â€˘ Osteocytes,osteoblasts & osteoclasts are the cellular crafts men performing the managerial roles of calcium regulation & bone homeostasis, physiological processes fundamental to modeling & remodeling. www.indiandentalacademy.com
Osteoclasts • Granulocytic – precursors found in bone marrow enter the circulation as monocytes , and through asynchronous fusion, produce a multinucleated cell with an average of 10 – 12 nuclei known as osteoclast. • Osteoclasts have a ruffled border, possess calcitonin receptors, produce tartarate resistant acid phosphatase. www.indiandentalacademy.com
• Interleukin 1,3,6& 11 and probably TNF – alpha along with transforming growth factor – alpha appear to be important modulators for development of osteoclasts. • Evidence appears to implicate a dynamic interplay between soluble factors, osteoblasts & osteoclasts. www.indiandentalacademy.com
1 – 25 – dehydroxy vitamin – D3 binds with osteoblasts Expression of osteoclast differentiation factor
Osteoclast progenitors that have been primed by exposure to soluble factors such as interleukins.www.indiandentalacademy.com
• When osteoblast disperse from bony surfaces, in response to PTH, an exposed osteoid – mineralised run away provides osteoclasts with an oppurtunity to attach. • Attachment involves surface adhesion molecules (integrins) & proteins. • Osteopontin , a sialophosphoprotein, secures osteoclast docking to bone through an arginine – glycine aspartic acid motif. www.indiandentalacademy.com
â€˘ The attachment perimeter is referred to as the zone of attachment & with in this zone, a ruffled border develops. â€˘ The ruffled border constitutes the resorptive teritory of the osteoclast where enzymatic breakdown of the bone surface occurs. www.indiandentalacademy.com
â€˘ The zone of attachment between the ruffled border & the bone isolates the surface microenvironment , enabling aditional enzymes such as carbonic anhydrase to decrease ph thus promoting solubilization of the inorganic matrix of Ca & P & exposing the organic matrix to these proteolytic enzymes. www.indiandentalacademy.com
• Osteoblasts are prompted to express modulators of osteoclastic activity following osteoblast receptor binding to either PTH or 1-25 dihydroxy vitamin – D3 . • This has been verified by invitro experiments revealing that these harmones have no effect on bone reorption when added to cultures containing only osteoclasts, however osteoclastic activity develops when osteoblasts are added. www.indiandentalacademy.com
organic 35 % of dry wt. Type I collagen. 10 % non collagenous proteins.ex:BMP Non collagenous proteins are PG or GAG Modulate cellular attachment.
60 â€“ 70 % of dry wt. 99% Ca, 85 % P, 40 â€“ 60 % Na & Mg
â€˘ During skeletal embryogenesis , homeostasis & repair , osteoblasts vectorially express an organic based product, osteoid, that is primarily composed of type â€“ I collagen & is the template for Ca & P deposition.
Soluble factors â€˘ In 1938 Levander stated that bone regeneration takes place as a result of some specific bone formation substance activating the non specific mesenchymal tissue.Later on the term osteoinduction is used to describe the same phenomenon. â€˘ These soluble factors especially bone morphogenic proteins are necessary for osteoinduction. www.indiandentalacademy.com
â€˘ BMPâ€™s are a group of morphogenic proteins that direct embryologic development of cells, tissues & organs in adition to performing crucial roles in post fetal physiology.
Precondition for orthodontic tooth movement â€˘ Precondition for this remodeling activity is inflammatory response. â€˘ Inflammation is local response of host to tissue injury by microbial material, chemical or physical stimulus. www.indiandentalacademy.com
Inflammation is characterized by redness, heat,swelling,pain & loss of function.
These visual changes are the result of
1. Vasodilatation with increased vessel permeability & blood flow. 2. Exudation of fluids. 3. Leukocyte migration into extra vascular spaces www.indiandentalacademy.com
â€˘ The spread of inflammatory response is propagated as well as amplified by
Chemical mediators â€˘
Also called permeability factors or endogenous mediators of increased vascular permeability.
The substances acting as chemical mediators of inflammation may be released from the cells, plasma or damaged tissue itself.
â€˘ They are classified as 1. Mediators released by cells 2. Mediators originating from plasma. www.indiandentalacademy.com
Mast cells, Basophils, Platelets
increase permeability & tissue damage
lysosomal enzymes prostaglandin leukotrienes, cytokines oxygen metabolites www.indiandentalacademy.com
inc permeability vasodilatation fever,tissue damage.
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Inflammatory mediators & orthodontic tooth movement
â€˘ Vascular & cellular inflammatory changes are mediated and ,maintained by a number of biochemical substances. â€˘ These mediators are detected in increased levels in dental tissues incident to orthodontic tooth movement and are secreted by existing inflammatory cells. www.indiandentalacademy.com
• Interleukin – 1 and tumor necrosis factor are pro inflammatory cytokines known to induce synthesis of various proteins which in turn elicit acute & chronic inflammation. • A marked increase in intensity for interleukin – 1 & TNF is noticed in the cells of PDL & alv bone of orthodontically moved cat canines, implying their activity in bone remodeling processes. www.indiandentalacademy.com
â€˘ Cells of nervous, immune, & endocrine systems become involved in the activation & response of the periodontal ligament & alveolar bone cells during tooth movement. â€˘ Orthodontic forces induce increased levels of prostaglandins & leukotrienes in both periodontal & bone cells. â€˘ According to Mostafa etal movement is mediated www.indiandentalacademy.com through local action of prostaglandins.
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• Arachidonic acid present in the membrane phospholipid of cells , can be released by phospholipidases activated by cellular damage or by any non destructive pertubation of the membrane. • Arachidonic acid is metabolized by two main enzyme path ways: cyclo-oxygenase, & lipo- oxygenase. • The products of arachidonic acid metabolism, namely PG’s of E & F series , prostacyclines & the leukotrienes are the integral components of the inflammatory reaction. www.indiandentalacademy.com
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m i h s a h l 1 0 A 0 2 O J A • Inflammatory cells produce cytokines which mediate various stages of inflammation. • Cytokines are proteins that act as signals between the cells of immune system. • They usually act locally but some act www.indiandentalacademy.com
• The various cytokines are interleukin – 1, interleukin – 6 & tumor necrosis factor – alpha. • IL-1 exists in 2 forms, alpha & beta, of which IL-1 beta is the one mainly involved in bone metabolism,stimulation of bone resorption, & inhibition of bone formation. • IL-1beta may act synergistically with TNF- alpha and is a powerful inducer of IL-6. www.indiandentalacademy.com
• Il-1beta,IL-6 and TNF-alpha were suggested to stimulate
bone resorption & bone cell replication. • Several positive and negative transcription factors function in a concerted manner to regulate the transcription of cytokines at the promoter or intron region. • It is also common for the transcription of cytokine genes to www.indiandentalacademy.com
initiate immediately on activation & to shut down quickly
Drug interaction • Pharmacological agents manipulate tooth movement in both directions. • Factors that enhance tooth movement are vitamin –D & direct injection of prostaglandin into periodontal ligament. • Drugs that inhibit tooth movement are frequently encountered. www.indiandentalacademy.com
â€˘ Two types of drugs are known to depress orthodontic tooth movement. They are 1. Bisphosphonates used in the treatment of osteoporosis. Ex : alendronate (fosmax.) 2. Prostaglandin inhibitors. Ex : drugs used in the treatment of arthritis like indomethacin. www.indiandentalacademy.com
Osteoporosis â€˘ It is a problem particularly encountered in post menopausal females but is associated with aging in both sexes. â€˘ Estrogen therapy , which is used frequently to prevent loss of bone in older women , has no impact on orthodontic treatment. â€˘ But pharmacological agents that inhibit bone resorption present a serious problem. www.indiandentalacademy.com
• Bisphosphonates are synthetic analogues of pyrophosphates that bind to hydroxyapatite in bone . • They act as specific inhibitors of osteoclast mediated bone resorption. • If orthodontic treatment is necessary in older patients it is better to switch over to estrogen at least temporarily. www.indiandentalacademy.com
Prostaglandin E inhibitors: • Prostaglandin E inhibitors are of two categories. They are • Corticosteroids & NSAIDs. • Other agents that have mixed agonist & antagonist effects on various prostaglandins. www.indiandentalacademy.com
â€˘ Prostaglandins are formed from arachidonic acid which in turn is derived from phospholipids. â€˘ Corticosteroids reduce prostaglandin synthesis by inhibiting the formation of arachidonic acid. â€˘ NSAIDsinhibit conversion of archidonic acid to prostaglandins. www.indiandentalacademy.com
• Other classes of drugs which reduce tooth movement are • Tricyclic antidepressants (doxepin,amitriptyline, imipramine.) • Anti arrhythmatic agents( procaine) • Anti malarial drugs ( quinine, quinidine, chloroquine.) • Anticonvulsant drug Phenytoin. • Tetracyclines ex: doxycycline (inhibit osteoclast recruitment) www.indiandentalacademy.com
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• Acetaminophen is suggested as analgesic of choice for relieving the discomfort associated with orthotreatment. • It is a very weak PG inhibitor. • Possess no significant anti- inflamatory effects. • Exact mechanism by which it relieves fever & pain is not known, it is believed to act in the CNS. • It has no effect on orthodontic tooth movement. www.indiandentalacademy.com
e o h e k l 6 e 9 a ci h AO M tal e • Study was done to compare the effect of Acetaminophen, ibuprofen, & misoprostol. • It was found ibuprofen significantly decreases PG synthesis in pdl of guinea pigs.there is a marked decrease in degree & rate of tooth movement. • Acetaminophen decreases peripheral PG production. But there is no significant effect on tooth movement. www.indiandentalacademy.com
â€˘ Misoprostol has insignificant inhibitory effect on local PGe2 production.the degree & rate of tooth movement increased. This acceleration is attributed to the enhanced bone resorbing activity of PGe1.
Conclusion: â€˘ Biochemical mediators have a significant role in tooth movement. Some have an accelerating effect & others have decelerating effects. However oral administration of these mediators to facilitate orthodontic treatment by enhancing tooth movement or for stabilisation requires further clinical study. www.indiandentalacademy.com
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