Effects of transforming growth factor beta-1 and bone morphogenetic protein-2 on osteoblasts at the bone-biomaterial interface
Abstract
The differentiated function of the osteoblast is to synthesize an extracellular matrix (ECM) that can be remodeled into mineralized bone. These functions can be further enhanced through the use of osteoinductive agents such as transforming growth facotor-beta-1 (TGF-β1) and bone morphogenetic protein-2 (BMP-2). The ECM then plays a further role in providing feedback to the osteoblast as to the suitability of its environment. This is achieved through interacting with the cellular ECM receptors, the integrins, to initiate signal transduction through the focal adhesion contact. Our studies have examined the effects of different orthopaedically relevant surfaces and treatments on the cellular events initiated by osteoblast association with the biomaterial. The studies are suggestive that the chemistry and topography of the substrate are active participants in the determination of the composition of the ECM and hence in osteoblast fate. Furthermore, osteoactive factors appear to amplify favorable interactions between osteoblasts and biomaterials. Based on our data and work by others, we have proposed that pathways activated by osteoblast adhesion through integrin occupancy regulate osteoblast maturation and mineralization. The importance of these early events and the role of the remodeling ECM and integrin signaling in the osteoblast maturation program are presently unknown and are under active investigation. As stated earlier, human bone undergoes continual remodeling through a regulated system of bone formation and resorption. Disruption of this tightly regulated cycle can result in a variety of diseased states including osteoporosis and osteoarthritis. Studies on the basic mechanism responsible for the pathogenesis of bone loss in osteoporosis have revealed both increased bone resorption and decreased bone formation. Anti-resorptive agents, estrogen and bisphosphonates, are currently being used as therapeutic modalities to minimize osteoporosis. Although these interventions are proving clinically effective in reducing bone resorption and maintaining bone loss, they have not been shown to be very effective in rebuilding new bone that has already been lost. It is believed that induction of new bone by bone formation stimulators may be able to augment current therapies by repairing and improving bone mechanical performance after the disease has become symptomatic. The work presented here specifically address bone augmentation at the bone-biomaterial interface. The interface is a man-made environment created while introducing biometals to stabilize bony structures or replace biological joints. Osseointegration remains critical to long term success at the bone-implant interface. Ongoing work in the laboratory is designed to elucidate the role of these enhanced interactions in osteoblast maturation and to optimize the early adhesive events to result in better osteoblast-biomaterial interaction. Ultimately, this information will be used to rationally design cell-based therapeutic paradigms to enhance biointegration of orthopaedic implants.
Subject Area
Molecular biology|Cellular biology|Biophysics|Physiology
Recommended Citation
Shah, Asit K, "Effects of transforming growth factor beta-1 and bone morphogenetic protein-2 on osteoblasts at the bone-biomaterial interface" (1999). ProQuest ETD Collection - Thomas Jefferson University. AAI9921831.
https://jdc.jefferson.edu/dissertations/AAI9921831
