以原位雜合反應探討雙磷酸鹽對骨骼再生之影響

Abstract

Bisphosphonates are effective drugs widely used to treat osteoporosis, Paget's disease, osteogenesis imperfecta and skeletal complications caused by metastatic cancer. Although generally well tolerated, there is a rare but potentially severe side effect, bisphosphonate related osteonecrosis of the jaw (BRONJ), first described in 2003. The clinical manifestation of the disease is exposure of bone, which is frequently accompanied by pain, soft tissue swelling or ulceration, suppuration, and abscess formation. BRONJ significantly impairs the quality of life and complicates dental treatment, such as tooth extraction and dental implant restorations. To date, the definitive mechanism of BRONJ still remains elusive. In this study, we use zebrafish as an in vivo animal model to dissect the etiology of BRONJ to unravel the underlying molecular mechanism using whole-mount in situ hybridization (ISH) on regenerative caudal fins after the amputation surgery. Our preliminary results suggest that bisphosphonates (alendronate) have no significant effects on gene expression related to mesenchymal cell proliferation and differentiation during the early stage of fin regeneration. However, further studies are needed to characterize the possible effects of bisphophobates during the entire process of fin regeneration. Eventually, we expect to unravel the detailed mechanism of BRONJ and shed light on potential treatment of this disease.