• BMB Reports
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• v.57 no.5
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• pp.256-261
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• 2024

In the context of aging, the susceptibility to infectious diseases increases, leading to heightened morbidity and mortality. This phenomenon, termed immunosenescence, is characterized by dysregulation in the aging immune system, including abnormal alterations in lymphocyte composition, elevated basal inflammation, and the accumulation of senescent T cells. Such changes contribute to increased autoimmune diseases, enhanced infection severity, and reduced responsiveness to vaccines. Utilizing aging animal models becomes imperative for a comprehensive understanding of immunosenescence, given the complexity of aging as a physiological process in living organisms. Our investigation focuses on Cisd2, a causative gene for Wolfram syndrome, to elucidate on immunosenescence. Cisd2 knockout (KO) mice, serving as a model for premature aging, exhibit a shortened lifespan with early onset of aging-related features, such as decreased bone density, hair loss, depigmentation, and optic nerve degeneration. Intriguingly, we found that the Cisd2 KO mice present a higher number of neutrophils in the blood; however, isolated neutrophils from these mice display functional defects. Through mass spectrometry analysis, we identified an interaction between Cisd2 and Calnexin, a protein known for its role in protein quality control. Beyond this function, Calnexin also regulates calcium homeostasis through interaction with sarcoendoplasmic reticulum calcium transport ATPase (SERCA). Our study proposes that Cisd2 modulates calcium homeostasis via its interaction with Calnexin and SERCA, consequently influencing neutrophil functions.

• Journal of Physiology & Pathology in Korean Medicine
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• v.27 no.4
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• pp.431-436
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• 2013

Bone homeostasis is maintained by co-ordination of bone-resorbing osteoclasts and bone-forming osteoblasts. Imbalance between osteoclasts and osteoblasts leads to many bone diseases such as osteoporosis, rheumatoid arthritis. Taxillus chinensis is a herb that has been widely used to improve bone health. However, the effect and mechanism of Taxillus chinensis extract on osteoclast differentiation and bone resportion has been unknown. Thus, We investigated the effect of Taxillus chinensis on expression of receptor activator of nuclear factor-${\kappa}B$ ligand (RANKL)-induced osteoclast differentiation and bone resorption. Also, the action of Taxillus chinensis on mechanisms relating to osteoclast differentiation was studied. In this results, we identified that Taxillus chinensis significantly inhibited RANKL-induced osteoclast differentiation and bone resportion. Moreover, Taxillus chinensis was suppressed the activation of NF-${\kappa}B$ in bone marrow macrophage treated RANKL and M-CSF. Taxillus chinensis was down-regulated the mRNA expression of c-Fos, nuclear factor of activated T-cells (NFAT)c1, osteoclast-associated receptor (OSCAR), tartrate-resistant acid phosphatase (TRAP). The cell adhesion-related molecules such as integrin ${\alpha}v$ and integrin ${\beta}3$, and the filamentous actin (F-actin) rings of mature osteoclasts-related molecules such as dendritic cell-specific transmembrane preotein (DC-STAMP) and cathepsin K are also suppressed. Taken together, these results indicated that Taxillus chinensis will be a good candidate to treat osteoclast-mediated bone diseases.

• Journal of Physiology & Pathology in Korean Medicine
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• v.28 no.1
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• pp.29-34
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• 2014

Bone homeostasis is maintained by balance between bone resorbing-osteoclasts and bone forming-osteoblasts. Excessive osteoclastic bone resorption plays a critical role in bone destruction in pathological bone diseases such as osteoporosis, rheumatoid arthritis, and periodontal disease. Many compounds derived from natural products have pharmacological applications and have therapeutic value for treating or preventing several bone diseases characterized by excessive bone resorption. To discover new compounds that can act as anti-resorptive agents, we screened for natural compounds that regulate osteclast differentiation, and found that water extract of Ziziphus Jujuba Mill (WEZJ) has inhibitory effects on osteoclast differentiation. In this study, WEZJ clearly inhibits the osteoclast differentiation in the presence of receptor activator of nuclear factor kB (RANKL), macrophage colony-stimulating factor (M-CSF) without cytoxicity by blocking activation of nuclear factor of activated T cells (NFAT)c1, and c-Fos. In signaling pathway, the phosphorylation of Akt, p38, c-Jun N-terminal kinases (JNK), extracellular signal-regulated kinases (ERK) and the expression of osteoclast-associated receptor (OSCAR), tartrate-resistant acid phosphates (TRAP), Integrin av, Integrin b3, Cathepsin K are suppressed, too. These result suggest that WEZJ may have therapeutic value for treating or preventing several bone diseases characterized by excessive bone destruction.

• Journal of Physiology & Pathology in Korean Medicine
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• v.26 no.4
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• pp.506-510
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• 2012

Bone homeostasis is regulated by the balance between bone-resorbing osteoclasts and bone-forming osteoblasts. Osteoporosis, rheumatoid arthritis and periodontal disease are related with up-regulated osteoclast formation and its activity. Gol-Swae-Bo(Drynariae Rhizoma) is widely used on skeletal disease. In this study, we sought to examine the effect of Drynariae Rhizoma in RANKL-induced osteoclast differentiation. The extract of Drynariae Rhizoma inhibited RANKL-induced osteoclast differentiation in a dose dependent manner without cytotoxicity. receptor activator of nuclear factor-${\kappa}B$ ligand(RANKL) mediated $I{\kappa}B$ degradation in bone marrow macrophages(BMMs). However, the extract of Drynariae Rhizoma inhibited RANKL induced $I{\kappa}B$ degradation in BMMs. And mRNA expression of OSCAR, TRAP, c-Fos and NFATc1 was suppressed by the extract of Drynariae Rhizoma. Moreover, the extract of Drynariae Rhizoma inhibited the protein expression of NFATc1 and c-Fos induced by RANKL. After all the analysis, these results suggest that Drynariae Rhizoma may be good candidate of medicine in the treatment of bone-related disease.

• Korean Journal of Medicinal Crop Science
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• v.23 no.2
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• pp.117-124
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• 2015

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 $100{\mu}g/ml$ of Gin significantly decreased cell viability of RANKL-induced osteoclast in RAW264.7 cell (p < 0.01). But, it was $50{\mu}g/ml$ 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.

• The Korean Journal of Oral and Maxillofacial Pathology
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• v.42 no.6
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• pp.159-165
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• 2018

The Hippo pathway was originally discovered in Drosophila by genetic screening and it has been shown to be conserved in various organisms including human. Until now, the essential roles of Hippo pathway in regulating cell proliferation, apoptosis, tumorigenesis, and organ size control is extensively studied. Currently, Mats1/2 (Mob1a/1b), one of the important components in Hippo pathway, mutant mice were generated which has abnormal phenotype such as resistance to apoptosis and spontaneous tumorigenesis. Of note, Mats1/2 mutant mice also showed dental malocclusion. Therefore, in this study, we have evaluated the bone phenotype of Mats1/2 mutant mice. Although the mRNA expressions of Mats1 or Mats2 were observed in both osteoclastogenesis and osteoblastogenesis, the increase of Mats1 level was most prominent during osteoblastogenesis. The RANKL-induced osteoclast differentiation from bone marrow-derived macrophages (BMMs) was unaltered upon Mats1/2 mutation; however, the osteoblast differentiation using calvarial pre-osteoblasts was significantly reduced in Mats1/2 mutant mice compare to that of wild type mice. In accordance with in vitro results, Mats1/2 mutant mice showed decreased bone volume as well as increased trabecular separation in ${\mu}CT$ analyses. These results may provide novel prospect of the probable linkage between Hippo pathway and bone homeostasis.

• Korean Journal of Pharmacognosy
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• v.53 no.1
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• pp.42-48
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• 2022

In order to maintain bone homeostasis, it is necessary to balance bone resorption and remodeling through the differentiation of osteoclasts that absorb old bone and osteoblasts that form new bone. However, bone resorption due to excessive osteoclast differentiation is a major cause of osteoporosis and controlling excessive osteoclast differentiation has been known as a treatment strategy for osteoporosis. Therefore, in this study, the effect of an ethanol extract of Sphaerotylus antarcticus Kirkpatrick, 1907 (SAE), polar-derived sponge with unknown biological activity, on the osteoclast differentiation process of RANKL-induced RAW264.7 cells and the generated ROS was evaluated. In the study results, SAE down-regulated the formation and function of RANKL-induced osteoclasts and osteoclast differentiation specific proteins, genes in a concentration-dependent manner. In addition, it was possible to confirm the result of restoring the lost antioxidant enzyme along with down-regulation of ROS generated by RANKL. Therefore, in this study, we propose the possibility of SAE as a potential regulator of osteoporosis due to excessive osteoclast differentiation and report the biological value of the diversity of marine-derived natural products by identifying the first biological activity against SAE that is not yet known.

• Korean Journal of Oriental Medicine
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• v.6 no.1
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• pp.123-132
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• 2000

Bone is continuously remodeled during adult life with the resorption of old bone by osteoclasts and its subsequent replacement by osteoblast. Bone homeostasis is maintained by a balance between activities of osteoblasts and osteoclasts, but an imbalance between resorption and formation results in bone diseases including osteoporosis. Osteoblasts line up on the bone surface, especially regions of new bone formation, lay down bone matrix (osteoid) in orderly lamellae and induce its mineralization. Thus, the increased activity of osteoblasts is helpful to treat and prevent osteoporosis. In this study, we examined whether 80% EtOH extract of yukmijiwhang-whan is capable of affecting osteoblast proliferation using human osteoblast-like cell line, MG-63 and Saos-2. In an in vivo experiment, extract of yukmijiwhang-whan was administered for 9 weeks to ovariectomized (OVX) rats. At necropsy, uterus weights were measured, and trabecular bone areas (TBAS) of tibia and the sixth lumbar vertebra were measured by bone histomorphology. The maximum cell proliferation of MG-63 caused by extract of yukmijiwhang-whan at $5\;{\times}\;10^{-6}\;mg/ml$ was approximately 115% compared with control. In Saos-2, cell proliferation was approximately 145% of control at $5\;{\times}\;10^{-4}\;mg/ml$ and maximum alkaline phosphatase (ALP) activity was approximately 143% of control at $5\;{\times}\;10^{-5}\;mg/ml$. In animal study, however, the tibia and lumbar TBAS of the yukmijiwhang-whan group did not increased than the OVX control group. In conclusion, the 80% EtOH extract of yukmijiwhang-whan increased proliferation of osteoblasts but did not prevent bone loss in OVX rats.

• Journal of the Korean Arthroscopy Society
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• v.9 no.2
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• pp.154-161
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• 2005

Purpose: to describe the histologic appearance of the type III bone bruise in knees which had sustained an acute anterior cruciate ligament (ACL) rupture. Materials and Method: Twenty-five patients who sustained acute ACL rupture were prospectively enrolled in this study. On MRI, 14 patients demonstrated type III bone bruise on lateral femoral condyle, and 11 patients didn't demonstrated bone bruise. Arthroscopic evaluation and biopsy of the articular cartilage and subchondral bone wert performed before ACL reconstruction. Histologic and immunohistochemical evaluations were done. Results: There was no difference between the bone bruise and control group in the hematoxylin-eosin staining for cell distribution, Masson's trichrome staining for collagen and immunohistochemical staining for type I and type II collagen (p>0.05). But in the safranin-O staining for glycosaminoglycan distribution, the bone bruise group had an evidence of decreased staining at the superficial and middle layers, compared with the control group (p<0.05). We also found fatty change of bone marrow in calcified zone of the bone bruise group with safranin-O staining. Conclusion: We suggest that the type III bone bruise found on MRI indicates a substantial damage to normal articular cartilage homeostasis, and may induce further damage of the articular cartilage.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.31 no.6
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• pp.544-549
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• 2009

Failure to use effective methods of reduction, fixation and immobilization may lead to osteomyelitis with the exposed necrotic bone, as the overzealous use of transosseous wires & plates that devascularizes bone segments in the compound comminuted fractures of mandible. Once osteomyelitis secondary to fractures has become established, intermaxillary fixation should be instituted as early as possible. Fixation enhances patient comfort and hinders ingress of microorganisms and debris by movement of bone fragments. Teeth and foreign materials that are in the line of fracture should be removed and initial debridement performed at the earliest possible time. Grossly necrotic bone should be excised as early as possible ; no attempt should be made to create soft tissue flaps to achieve closure over exposed bone. The key to treatment of chronic osteomyelitis of the mandible is adequate and prolonged soft tissue drainage. If good soft tissue drainage is provided over a long period, sequestration of infected bone followed by regeneration or fibrous tissue replacement will occur so that appearance and function are not seriously altered. Localization and sequestration of infected mandible are far better performed by natural mechanism of homeostasis than by cutting across involved bone with a cosmetic or functional defect. As natural host defenses and conservative therapy begin to be effective, the process may become chronic, inflammation regresses, granulation tissue is formed, and new blood vessels cause lysis of bone, thus separating fragments of necrotic bone(sequestra) from viable bone. The sequestra may be isolated by a bed of granulation tissue, encased in a sheath of new bone(involucrum), and removed easily with pincettes. This is a case report of the long-term conservative drainage care in osteomyelitis associated with mandibular fractures.