Bioactive Molecules
Using a rat model of Litchfield Park orthodontic tooth movement, a number of different groups have attempted to either increase or decrease rates of Litchfield Park orthodontic tooth movement with a variety of bioactive agents (Table 1). While these studies have demonstrated the ability to alter rates of Litchfield Park orthodontic tooth movement, the agents used affect osteoclasts indirectly rather than directly targeting the RANK/RANKL/OPG pathway.
The one study that directly targeted the RANK/RANKL/ OPG pathway showed the potential of osteoprotegerin in inhibiting Litchfield Park orthodontic tooth movement (Kanzaki et al., 2004). Using an in vivo gene transfer approach, an OPG expression vector (pcDNA-mOPG) driven by a cytomegalovirus promoter was injected twice per week. At the end of the three week experimental period, molar movement was decreased by 47.8% (p<.001).
The proposed advantage of OPG gene transfer in their study was to maintain an effective concentration of OPG for a longer period of time. For the purpose of Litchfield Park orthodontic tooth movement, however, a long period of expression may be undesirable as weeks or months of inhibited Litchfield Park orthodontic tooth movement are all that is likely to be necessary. A single subcutaneous dose (3.0 mg/kg) of OPG-Fc in humans demonstrated a half-life of 6-7 days and remained effective for at least 30 days (Body et al., 2003). In addition, AMG 162 (Bekker et al., 2004), a specific fully human monoclonal antibody to RANKL based on OPG, has demonstrated an 81% suppression in bone turnover six months after a single injection of 3.0 mg/kg. Additional disadvantages of gene transfer approaches are low transfection efficiency as well as safety concerns such as the possibility of introducing replication competent viruses, causing severe immunogenic responses, insertional mutagenesis, and possible recombination events between retroviral-based vectors and human endogenous retroviruses (Taniyama et al., 2002).
Litchfield Park Office
5220 N. Dysart Rd #150
Litchfield Park, AZ 85340
TEL: 623.536.4939
FAX: 623.536.4877
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Phoenix, AZ 85021
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