Computed tomography evaluation of risk factors for an undesirable buccal split during sagittal split ramus osteotomy.

Sagittal split ramus osteotomy (SSRO) sometimes induces an irregular split pattern referred to as a bad split. We investigated the risk factors for bad splits in the buccal plate of the ramus during SSRO. Ramus morphology and bad splits in the buccal plate of the ramus were assessed using preoperative and postoperative computed tomography images. Of the 53 rami analyzed, 45 had a successful split, and 8 had a bad split in the buccal plate. Horizontal images at the height of the mandibular foramen showed that there were significant differences in the ratio of the forward thickness to the backward thickness of the ramus between patients with a successful split and those with a bad split. In addition, the distal region of the cortical bone tended to be thicker and the curve of the lateral region of the cortical bone tended to be smaller in the bad split group than in the good split group. These results indicated that a ramus shape in which the width becomes thinner towards the back frequently induces bad splits in the buccal plate of the ramus during SSRO, and more attention should be paid to patients who have rami of these shapes in future surgeries.

Cathepsin K degrades osteoprotegerin to promote osteoclastogenesis in vitro.

Osteoblasts produce the receptor activator of nuclear factor-kappa B ligand (RANKL) and osteoprotegerin, the inducer and the suppressor of osteoclast differentiation and activation. We previously proposed that the degradation of osteoprotegerin by lysine-specific gingipain of Porphyromonas gingivalis and neutrophil elastase is one of the mechanisms of bone resorption associated with infection and inflammation. In the present study, we found that cathepsin K (CTSK) also degraded osteoprotegerin in an acidic milieu and the buffer with a pH of 7.4. The 37 k fragment of osteoprotegerin produced by the reaction with CTSK was further degraded into low molecular weight fragments, including a 13 k fragment, depending on the reaction time. The N-terminal amino acid sequence of the 37 k fragment matched that of the intact osteoprotegerin, indicating that CTSK preferentially hydrolyzes the death domain-like region of osteoprotegerin, not its RANKL-binding region. The 13 k fragment of osteoprotegerin was the C-terminal 13 k portion within the RANKL-binding region of the 37 k fragment. Finally, CTSK restored RANKL-dependent osteoclast differentiation that was suppressed by the addition of osteoprotegerin. Collectively, CTSK is a possible positive regulator of osteoclastogenesis.

8-Nitro-cGMP suppresses mineralization by mouse osteoblasts.

Nitric oxide and reactive oxygen species regulate bone remodeling, which occurs via bone formation and resorption by osteoblasts and osteoclasts, respectively. Recently, we found that 8-nitro-cGMP, a second messenger of nitric oxide and reactive oxygen species, promotes osteoclastogenesis. Here, we investigated the formation and function of 8-nitro-cGMP in osteoblasts. Mouse calvarial osteoblasts were found to produce 8-nitro-cGMP, which was augmented by tumor necrosis factor-α (10 ng/ml) and interleukin-1ß (1 ng/ml). These cytokines suppressed osteoblastic differentiation in a NO synthase activity-dependent manner. Exogenous 8-nitro-cGMP (30 µmol/L) suppressed expression of osteoblastic phenotypes, including mineralization, in clear contrast to the enhancement of mineralization by osteoblasts induced by 8-bromo-cGMP, a cell membrane-permeable analog of cGMP. It is known that reactive sulfur species denitrates and degrades 8-nitro-cGMP. Mitochondrial cysteinyl-tRNA synthetase plays a crucial role in the endogenous production of RSS. The expression of osteoblastic phenotypes was suppressed by not only exogenous 8-nitro-cGMP but also by silencing of the Cars2 gene, indicating a role of endogenous 8-nitro-cGMP in suppressing the expression of osteoblastic phenotypes. These results suggest that 8-nitro-cGMP is a negative regulator of osteoblastic differentiation.

Possible involvement of elastase in enhanced osteoclast differentiation by neutrophils through degradation of osteoprotegerin.

Neutrophils are one of the most abundant leukocytes in the sites of lesion of inflammatory diseases such as periodontitis and rheumatoid arthritis. These diseases are accompanied by bone loss, which worsens the quality of life of the patients. However, the role of neutrophils in the inflammatory bone loss has not been fully investigated. In the present study, we found that human neutrophils enhanced osteoclast differentiation from mouse bone marrow cells co-cultured with mouse osteoblasts in the presence of active vitamin D3. The enhanced osteoclast differentiation was significantly suppressed by elastatinal, a synthetic inhibitor of neutrophil elastase. Also, we found that human neutrophils degraded human recombinant osteoprotegerin (OPG), a decoy receptor for nuclear factor κB (RANK) ligand (RANKL), the essential osteoclast differentiation-inducing factor, expressed by osteoblasts. Degradation of OPG by neutrophils was suppressed by human α1-protease inhibitor, the major endogenous inhibitor of neutrophil elastase. Recombinant human neutrophil elastase degraded human OPG in its death domain-like region. These results indicated that the degradation of OPG by elastase contributed at least in part to the enhanced osteoclast differentiation by neutrophils. There is a possibility that neutrophils play an important role in inflammatory bone loss.