THE FUNCTION OF COX-2 IN MECHANOTRANSDUCTION

University Of Texas Hlth Sci Ctr Houston, Houston TX

Investigators

Abstract

Mechanotransduction, or the process by which cells translate physical stimuli into biochemical signals, is central to many dental therapies including orthodontic movement of teeth, periodontal therapy, distraction osteogenesis, stabilization of removable prostheses, and more recently, placement and restoration of dental implants. The rationale for using dental implants or natural roots as overdenture abutments is to maintain a pathway for mechanical forces to be transmitted to the bone cells, thereby preventing bone loss. Physiological remodeling of alveolar bone is a tightly regulated process requiring an optimal level of mechanical stimulation to the bone cells. The long range goals of these studies are to understand how bone cells integrate information about mechanical pressures on the cells and the extracellular matrix (ECM), and subsequently transmit these signals to regulate growth, differentiation and gene expression. New evidence suggests that the synthesis of prostaglandins by COX-2 is an essential early event in mechanotransduction. Thus, this study focuses on how increased levels of COX-2 synthesized prostaglandins trigger a biochemical cascade of events through: 1) intermediate steps that alter the transcription of signal transduction or transcription factors, and 2) later steps that result in increased levels of bone matrix molecules. To do this, a combination of in vitro and in vivo studies will be performed. An in vitro mechanical loading system will be used to generate mRNAs from mechanically loaded cells, non-loaded cells, and mechanically loaded cells treated with COX2 inhibitors. This will identify candidate genes that may be involved in COX-2 mediated mechanotransduction pathways. An in vivo mechanical loading system will be used to compare the effects of mechanical loading on bone formation, as measured by calcein uptake levels, between COX-2 null allele, heterozygote, and wildtype mice. Knowledge gained from these studies will provide insight into the mechanisms of mechanotrransduction and lay the groundwork for possible pharmacological and mechanical modalities to regulate alveolar bone remodeling in a predictable manner during dental treatments.