2009 Fiscal Year Final Research Report
EFFECT OF CASPASE 3 ON BONE METABOLISM
| Project/Area Number |
19592159
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Functional basic dentistry
|
|---|
| Research Institution | Showa University |
|---|
Principal Investigator |
AMANO Hitoshi Showa University, 歯学部, 准教授 (90212571)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
TANAKA Sakae 東京大学, 医学部, 准教授 (50282661)
TAKAHASHI Katsuhiko 星薬科大, 薬学部, 准教授 (80307066)
|
|---|
| Project Period (FY) |
2007 – 2009
|
| Keywords | カスパーゼ3 / 破骨細胞 / アポトーシス |
|---|
| Research Abstract |
Apoptosis is defined as programmed cell death, which is characterized by cell contraction and fragmentation, and nuclear aggregation and fragmentation. Various types of molecular signaling control Apoptosis. Caspase3, a type of cysteine protease, can be activated by stimulus, leading to degradation of a broad range of intracellular substances such as PARP and to induction of apoptosis. Approximately one-half of osteoblasts involved in bone formation undergo apoptosis during the process of transformation into osteocytes when embedded within the bone. In addition, osteoclasts are known to enter apoptosis away from the bone surface after bone resorption. Apoptosis in bone-related cells is considered an essential metabolic system in bone structure ; moreover, Caspase3 may play a significant role in this process. We investigated the role of Caspase3 via utility of mice carrying a Caspase3 gene deficiency. Following completion of visual observation and x-ray photography of mouse skulls (8 we
… More
eks of age), skullcaps from mice with the gene deficiency exhibited quaquaversal (dome-like) formation characterized by an obtuse angle between the eye-ear plane and the anteroposterior diameter of the occipital skull-base in comparison with the wild type ; consequently, growth suppression of the skull was apparent. Moreover, in mice with the gene deficiency, increased membranous ossification and mandibular prognathism were detected with increasing age. Newborn tibias, following fixation as tissue sections by conventional fixation, were decalcified, embedded in paraffin. Mice with the gene deficiency displayed elevated osteoblast OPG mRNA expression in comparison to the wild type. Increased calcification in osteoblasts carrying the gene deficiency was also demonstrated in vitro. There was no significant difference in osteoclast formation between Caspase 3-/- mice and their littermate. In constrast, caspase3 -/- osteoclast increased bone resorbing activity. This study confirmed abnormal skull formation with increased bone formation and resorption in mice lacking the Caspase3 gene, which controls apoptosis. Caspase3 gene maintains a delicate balance between bone formation and bone resorption ; moreover, it adjusts normal skull development via control of apoptosis in osteoblasts and osteoclasts. Less
|
