파골세포양 거대세포형 미분화 암종은 췌장암의 1%만을 차지하는 흔치 않은 암종으로 알려져 있다. 저자들은 39세 남자에게서 진단된, 수술 및 항암치료를 시행한 1예를 소개하고자 한다.

The bones of the human body support the structures of the body and provide protection for a person’s internal organs. Bone metabolic diseases are on the rise due to a significant increase in life expectancy over a short period of time. Therefore, we investigated the osteoblast differentiation promoting and osteoclastogenesis inhibitory activities of fermented Benincasa hispida cong. (HR1901-BS, HR1901-BSaf). We evaluated the alkaline phosphatase (ALP) activity of MC3T3-E1 mouse calvarial-derived osteoblasts. We also evaluated expression of ALP, osteocalcin (OCN), and runt-related transcription factor 2 (Runx2), which regulate osteoblast differentiation. To assess effects on osteoclast formation, tartrate-resistant acid phosphatase (TRAP) activity in RAW264.7 cells was analyzed. ALP activity increased by 121-136% and 140-156%, respectively in the presence of HR1901-BS and HR1901- BSaf. Expression of osteoblast differentiation factor also increased significantly. We also confirmed that HR1901-BS and HR1901-BSaf decreased TRAP activity in osteoclasts by 35-47% and 23-39%, respectively. Our results showed that fermented Benincasa hispida cong. (HR1901-BS, HR1901-BSaf) increase bone mineralization and osteoblast differentiation activity in MC3T3-E1 cells, and inhibit bone resorption activity in RAW264.7 cells. In conclusion, fermented Benincasa hispida cong. (HR1901-BS, HR1901-BSaf) can be used as an effective natural resource for preventing and treating bone-related diseases.

본 연구는 방사선 육종 차조기와 백출 복합물의 조골세포 분화 활성 및 파골세포 형성 억제를 조사하였다. 차조기와 백출 복합물은 MG-63 세포에서 ALP 활성 및 arlizarin red 염색을 확인하였고 조골세포 형성의 영향은 RAW 264.7 세포에서 TRAP 활성과 TRAP 염색을 진행하였다. 세포 독성 시험에서 차조기와 백출 복합물은 50 ㎍/㎖ 농도 이하에서 안전한 것으로 확인되었다. ALP 활성 및 골석회화 형성 능력은 대조군보다 활성이 낮았으나, 파골세포에서 TRAP 활성을 유의적으로 감소시켰으며, 효과적으로 TRAP(+) 다핵세포를 억제하였다. 따라서 차조기와 백출 복합물은 골 흡수 억제 활성을 향상시켜 뼈 관련 질환의 예방 및 치료에 효과적인 것으로 보여진다.

Connective tissue growth factor (CTGF, CCN2) is one of the multi-functional secreted proteins which belong to CCN family of cysteine-rich growth factors. CTGF is known to have pivotal roles in embryonic endochondral ossification but its role in relevance to periodontitis is never been determined. To identify new molecular mediators associated with periodontitis-induced bone resorption, we have analyzed publicly available GEO database and found the markedly augmented CTGF mRNA expression in periodontitis gingival tissues. The existence of CTGF significantly enhanced mature osteoclasts survival which accompanied by reduction in TUNEL-positive nuclei and PARP cleavage. These results may provide another line of evidence the CTGF mediated prolonged osteoclast survival and subsequent increased bone resorption in the periodontitis patients.

췌장의 파골세포양 거대세포 미분화 암종은 그 발생 빈도는 드물지만 높은 악성도를 가지는 외분비 췌장암이다. 췌장 의 파골세포양 거대세포 미분화 암종은, 복부 전산화단층촬 영에서 괴사와 출혈을 동반한 낭성 및 고형 종괴의 소견을 보이며, 다른 췌장의 낭성 종양과 감별이 필요하다. 현재까 지 명확하게 정립된 치료법은 없으며, 조기 진단 및 종양의 완전 절제만이 생존률 향상을 가져온다고 보고되고 있다. 본 증례는 58세 남성 환자에서 발생한 췌장의 파골세포양 거대 세포 미분화 암종이 수술 및 항암치료에도 불구하고 연조직 전이로 진행하여 사망한 1예로 문헌고찰과 함께 보고한다.

염증성 사이토카인은 파골세포형성과정에서 중요한 요인이며, 뼈의 흡수는 자주 골다공증과 연결된다. 설포라판은 보로콜리의 화뢰로 부터 분리된 물질로 염증성 사이토카인을 억제한다고 알려져 있다. 본 실험 에서는 Receptor activator of nuclear factor kappaB ligand(RANKL)로 자극된 세포에서 설포라판이 파 골세포 형성 억제에 대한 효과를 측정하였다. 설포라판은 대식세포인 RAW 264.7 세포에서 파골세포 특이 마커 유전자인 tartrate-resistant acid phosphatase(TRAP), Cathepsin K, matrix metalloproteinase 9 (MMP-9), calcitonin receptor을 저해하였으며, TRAP, MMP-9, tumor necrosis factor receptorassociated factor 6(TRAF6)와 전사인자인 nuclease factor of activated T cells(NFATc1)의 단백질 발현 과 RANKL로 자극하였을 때 전자인사인 nuclear factor kappaB(NF-kappaB)의 전사활성도 억제 하였다. 이와 같은 결과로 설포라판이 NF-kappaB의 전사활성 억제뿐만 아니라, 파골세포형성인자(TRAP, cathepsin K, MMP-9, calcitonin, NFATc1)와 NFATc1의 발현을 억제시키는 효과가 있음을 확인하였다.

실크단백질은 누에고치를 구성하는 단백질로서 누에가 생합성하는 천연단백질 이다. 화학적 처리에 의하여 실크단백질은 인체 활성을 갖는 특성이 있는 것으로 최 근 보고되고 있다. 일반적으로 뼈는 신생골을 만드는 조골세포와 오래된 뼈를 흡수 하는 파골세포간의 균형적인 역할에 의하여 유지된다. 파골세포와 조골세포의 역 할에 영향을 줌으로써 골다공증 등 뼈와 관련된 질환의 예방 및 치료에 활용될 수 있다. 화학적으로 처리된 실크단백질이 파골세포의 분화에 영향이 미치는 것으로 보고되었다. 파골세포에 미치는 실크단백질의 효과에 대한 영향을 살펴보기 위하 여 receptor activation of nuclear factor κB ligand (RANKL), 파골세포 특이 유전자 (matrix metalloproteinase-9 (MMP-9), cathepsin-K, calcitonin receptor (CTR)), mitogen-activated protein kinase (MAPK), nuclear factor-κB (NF-κB) transcription factors (nuclear factor of activated T cells c1 (NFATc1))의 발현을 분석하였다.

Hydroxyapatite (HAp) and biphasic calcium phosphate (BCP) nano powders were synthesized using the microwave-assisted synthesis process dependent on pH and microwave irradiation time. The average size of a powder was less than 100 nm in diameter. Through in-vitro cytotoxicity tests by an extract dilution method, the HAp and BCP nano powders have shown to be cytocompatible for L-929 fibroblast cells, osteoblastlike MG-63 cells and osteoclast-like Raw 264.7 cells. The activation of osteoblast was estimated by alkaline phosphatase (ALP) activity. When the HAp and BCP were treated to MG-63 cells, alkaline phosphatase activities increased on day 3, compared with those of the untreated cells. Also, the collagen fibers increased when the HAp and BCP powders suspension were treated to MG-63 cells, compared to those of the untreated cells. Quantitative alizarin red S mineralization assays showed a trend toward increasing mineralization in osteoblast cultured with powder suspension. In conclusion, hydroxyapatite and biphasic calcium phosphate appeared to be a bone graft substitute material with optimal biocompatibility and could be further applied to clinical use as an artificial bone graft substitute.

Background : Osteoclasts are differentiated from the monocytes/macrophages of hematopoietic cells, that excessive activities of bone-resorbing giant cells leads to pathological bone diseases such as osteoporosis (contained rheumatoid arthritis and autoimmune arthritis). Therefore, it is very important to suppress loss of bone mass by deactivation of osteoclast differentiation. In this context, we evaluated for the effects of black ginseng (BG) extract on TRAP activity, proliferation and differentiation in RANKL-induced osteoclastic RAW264.7 cells. Methods and Results : The aim of this study is to figure out the potential anti-osteoporosis effects and the underlying mechanism of BG extract in RANKL-induced osteoclastic RAW264.7 cells. The ginsenoside Rg3, Rg5, Rk1 and Rh4 content of BG was increased more than Red ginseng (RG). The extracts of BG markedly reduced the activity of tartrate-resistant acid phosphatase-positive (TRAP+) multinucleated cells from osteoclastic RAW264.7 cells, without cytotoxicity. BG clearly inhibited RANKL-induced osteoclast differentiation by decreased calcitonin and TRAP (p < 0.01). Furthermore, ginseonside Rg5 and Rk1 significantly inhibited TRAP activity in formation of osteoclastic differentiation (p < 0.01). It is also found that Ginseonside Rg5 and Rk1 mixture more inhibits osteoclast differentiation activity. Conclusion : Our results suggest that Black ginseng extract has an anti-osteoporosis effects in bone disease when administered as a food supplement and has potential as a therapeutic agent for osteoporosis.

Background : This study aimed to determine the anti-osteoclastogenic effects of extracts from CK berry’s and identify the underlying mechanisms in vitro. Methods and Results : Reactive oxygen species (ROS) are signal mediators in osteoclast differentiation. AM extracts inhibited ROS production in RAW264.7 cells in a dose-dependent manner and exhibited strong radical scavenging activity. The extracts also attenuated the number of tartrate-resistant acid phosphatase (TRAP)-positive multinucleated osteoclasts. To attain molecular insights, the effect of the extracts on the signaling pathways induced by receptor activator of nuclear factor kappa B ligand (RANKL) were also investigated. RANKL triggers many transcription factors through the activation of mitogen-activated protein kinase (MAPK) and ROS, leading to the induction of osteoclast-specific genes. The extracts significantly suppressed RANKL-induced activation of MAPKs, such as extracellular signal-regulated kinase (ERK), c-Jun-N-terminal kinase (JNK), and p38, and consequently led to the downregulation of c-Fos and nuclear factor of activated T cells 1 (NFATc1) protein expression which ultimately suppress the activation of the osteoclast-specific genes, cathepsin K, TRAP, calcitonin receptor, and integrin β3. Conclusion : In conclusion, our findings suggest that AM extracts inhibited RANKL-induced osteoclast differentiation by downregulating ROS generation and inactivating JNK/ERK/p38, nuclear factor kappa B (NF-κB)-mediated c-Fos and NFATc1 signaling pathway.

Background : Capsaicin is an active component of chili peppers, which are plants belonging to the genus Capsicum. Research reported capsaicin has antioxidant and anti-inflamatory activity and osteoclast lineages are very susceptible to oxidative stress, as osteoclasts are produced by increased-generation of intracellular ROS and osteoclasts are activated by ROS. Therefore, our study was evaluated the influence of intracellular oxidative stress such as increased ROS level on RANKL-mediated osteoclast differenciation. Methods and Results : Capsaicin showed a good free radical scavenging activity at in-vitro antioxidant activity. The inhibitory effect of osteoclast differentiation on capsaicin was confirmed. Osteoclast differentiation from murine macrophage RAW 264.7 cells was induced by RANKL. The effect of capsaicin on receptor activator of nuclear factor-κB (NF-κB) ligand (RANKL)-induced osteoclast differentiation was demonstrated using a tartrate-resistant acid phosphatase (TRAP) assay and TRAP staining. Capsaicin showed an inhibitory effect on TRAP activity. The TRAP staining showed that the number of TRAP positive osteoclasts was reduced in capsaicin-treated cells. Conclusion : Capsaicin revealed an inhibitory effect in osteoclast differentiation induced by RANKL. These results suggest that capsaicin may have a beneficial effect for the prevention or treatment of osteoclast caused bone diseases such as osteoporosis.

Background : Osteoclasts as multinucleated cells originate from hematopoietic monocyte/ macrophage precursor cell, shows the bone absorption through the commitment, differentiation, fusion, and bone resorption stages by regulation of M-CSF and RANKL. It has been reported a significant negative correlation between the increase of oxidative stress and the bone density, and when RANKL reaction to the osteoclasts precursor cells is mainly generated ROS is due to increased activity of NADPH oxidase1 (NOX1), and these ROS act as a factor which promotes osteoclasts differentiation. Thus, RANKL signaling process is important that excessive osteoclast formation and differentiation inhibited through the regulation of each step. Methods and Results : F3570 ethanol extract showed relatively high activity at in-vitro antioxidant activity. F3570 water extract inhibited ROS generation in RAW 264.7 cells stimulated with H2O2 and RANKL, even at low concentrations. The inhibitory effect of osteoclast differentiation on F3570 water extract was confirmed that shown through NF-κB pathway, MAPK pathway including ERK and JNK. F3570 ethanol extract is considered to be regulated by the p38 MAPK and the other signaling pathway. Also, F3570 both water and ethanol extract were significantly reduced gene expression such as TRAP, calcitonin receptors and integrin β3 of RANKL-induced mature osteoclast in the bone resorption stage. Conclusion : Through this study, F3570 extract revealed an outstanding inhibitory effect and signaling mechanisms in osteoclast differentiation induced by RANKL. These results suggest that F3570 is bone diseases associated with aging or osteoporosis caused by menopause in an aging society is expected to be a superior candidate for the treatment or the prevention

Osteoporosis induces a bone mineral density loss due to imbalance of bone homeostasis that is achieved by osteoclasts (which are involved in bone resorption) and osteoblasts (which are involved in bone formation). Thus, this study was performed to evaluate the effects of hot water extract of the Achyranthes bidentata Blume (ABB) and Panax ginseng (Gin) on osteoclast and osteoblast differentiation. In this study, there was no cytotoxicity by ABB, 50 and 100 μg/ml of Gin significantly decreased cell viability of RANKL-induced osteoclast in RAW264.7 cell (p < 0.01). But, it was 50 μg/ml of ABB and Gin mixtures increased due to protective action of ABB. Furthermore, Gin contained groups (Gin, ABB and Gin mixtures) were inhibitory effects on osteoclast differentiation and bone resorption, and increased in osteoblast differentiation activity. Gin clearly inhibited RANKL-induced osteoclast differentiation by decreased calcitonin and TRAP (p < 0.01). Also, these extracts significantly increased calcium accumulation formation of osteoblastic differentiation reagents-induced osteoblast in MC3T3-E1 cell (p < 0.05). These results suggest that ABB and Gin mixtures may be a potential as drug for the treatment of osteoporosis.