Bone and joint disorders caused by increased autoimmune bone resorption debilitate 27 million Americans who live with osteoarthritis (OA). The lifetime risk of developing OA of the knee and hip is about 46% and 25%, respectively. The normal function of Osteoclasts is to remodel bone. When osteoclasts are overly active as in OA, they resorb too much bone causing constant pain, reduced limb mobility, and reduction in quality of life. The use of implants to replace joints can be successful, but they can also be attacked by osteoclasts. Unfortunately, there is no therapeutic intervention that can fully prevent osteoclasts from resorbing bone and causing OA or osteoporosis (OP). Osteoclasts are difficult to study because of their short lifespan: The rationale for this research is to create longer-living osteoclast cells that can be used to identify osteoclast inhibitors as a step towards developing a drug to prevent or reverse OA and OP.
In addition, this project will investigate the ability of implants to resist attachment by osteoclasts. A total of 92 treatment groups and 1020 individual specimens will be created in this study to pursue four specific aims: i. Create immortalized osteoclast cell lines using mouse macrophages (RAW264.7 cells) and human monocytes. ii. Measure the ability of potential osteoclast inhibitors to prevent the degradation of bone and collagen matrix. iii. Investigate the effectiveness of hormones such as estrogen, to increase or reduce the osteoclast-mediated degradation of bone and collagen matrix. iv. Develop strategies to inhibit osteoclast attachment to implant surfaces. Quantitative data will be collected and statistically evaluated using two-way analysis of variance. The significance of this study is that it will give hope to millions of OA and OP sufferers seeking a therapeutic intervention and contribute to the development of implant surfaces that can resist failure caused by osteoclast attachment.