• Clinical and Experimental Pediatrics
• /
• v.45 no.2
• /
• pp.256-260
• /
• 2002

Bone marrow necrosis is a rare complication of a variety of diseases affecting the marrow. The cause and incidence are unknown, and reports of treatment response are rare. We describe a case of relapsed acute mixed type leukemia with bone marrow necrosis. The patient was a 10 year old female diagnosed with acute mixed type leukemia four years ago. She had been on second remission state for 1 year, presented with severe back pain, tenderness in lower extremities, low-grade fever and general weakness. Her level of serum lactic dehydrogenase on admission was increased. Bone marrow aspiration from both posterior iliac crest showed marrow necrosis. Subsequent examination showed the same feature. Hip MRI showed heterogenous low signal intensity in both iliac bone on T-1 weighted image and heterogenous high signal intensity on T-2 wieghted image. Remission induction therapy was started but she expired on 59th hospital day due to the complication of sepsis.

• Archives of Pharmacal Research
• /
• v.19 no.5
• /
• pp.368-373
• /
• 1996

Nitric oxide (NO) is synthesized by various cells involved in inflammatory reactions and may then act on mast cells. In the present work, we attempted to clarify the role of this molecule on the proliferation of mouse bone marrow derived-mast cells (BMMC). Swiss 3T3 fibroblastsproduced nitrite ($NO_{2}$) and nitrate ($NO_{3}$) upon treatment with interferon ${\gamma}$(IFN-${\gamma}$). This formation was dependent of L-arginine and could be inhibited by the -L-arginine analogue $N^{G}$-monomethyl-L-arginine ($N^{G}$MMA). The effect of IFN-g was drastically invreased by cotreatment with tumor necrosis factor g(IFN-g). BMMC were maintained in vitro for as long as 30 days when cocultured with Swiss 3T3 fibroblasts. coculture with $N^{G}$MMA, significantly increased the number of BMMC. These results indicate that NO involves the inhibition of proliferation of BMMC when cocultured with Swiss 3T3 fibroblasts.

• Journal of Veterinary Science
• /
• v.19 no.6
• /
• pp.744-749
• /
• 2018

Dapsone, an antibiotic, has been used to cure leprosy. It has been reported that dapsone has anti-inflammatory activity in hosts; however, the anti-inflammatory mechanism of dapsone has not been fully elucidated. The present study investigated the anti-inflammatory effects of dapsone on bone marrow cells (BMs), especially upon exposure to lipopolysaccharide (LPS). We treated BMs with LPS and dapsone, and the treated cells underwent cellular activity assay, flow cytometry analysis, cytokine production assessment, and reactive oxygen species assay. LPS distinctly activated BMs with several characteristics including high cellular activity, granulocyte changes, and tumor necrosis factor alpha ($TNF-{\alpha}$) production increases. Interestingly, dapsone modulated the inflammatory cells, including granulocytes in LPS-treated BMs, by inducing cell death. While the percentage of Gr-1 positive cells was 57% in control cells, LPS increased that to 75%, and LPS plus dapsone decreased it to 64%. Furthermore, dapsone decreased the mitochondrial membrane potential of LPS-treated BMs. At a low concentration ($25{\mu}g/mL$), dapsone significantly decreased the production of $TNF-{\alpha}$ in LPS-treated BMs by 54%. This study confirmed that dapsone has anti-inflammatory effects on LPS-mediated inflammation via modulation of the number and function of inflammatory cells, providing new and useful information for clinicians and researchers.

• International Journal of Oral Biology
• /
• v.31 no.2
• /
• pp.67-72
• /
• 2006

Nitric oxide(NO) is a labile, uncharged, reactive radical that functions as a sensitive mediator of intercellular communication in diverse tissues. It has been reported that NO is produced by osteoblast and these results may suggest that NO is integrally involved in the regulation of osteoclast formation and osteoclast resorption activity by osteoblastic cells. We examined the effect of cytokines on NO release by mouse bone marrow cell. We also examined the effects of cytokines and sodium nitroprusside(SNP) on the formation of osteoclast-like cell from mouse bone marrow cells in culture. Cytokines stimulated NO production of mouse bone marrow cells, and N-nitro-L-arginine methyl ester, a specific inhibitor of NO synthase, suppressed the cytokine-induced NO production. SNP showed dual action in the generation of osteoclasts. The addition of $30{\mu}M$ SNP inhibited the formation of tartrate resistant acid phosphatase(TRAP)(+) multinucleated cell, whereas lower concentration($3{\mu}M$) of SNP enhanced it. Although the precise action of NO remains to be elucidated in detail, the action of NO in osteoclast generation in our studies seems to be associated, at least in part, with bone metabolism and bone pathophysiology.

• Journal of Life Science
• /
• v.16 no.7 s.80
• /
• pp.1207-1213
• /
• 2006

Tumor necrosis $factor-{\alpha}\;(TNF-{\alpha})$ has been implicated in skeletal diseases by promoting bone loss in inflammatory bone diseases. In the present study, we examined the effects of $TNF-{\alpha}$ on osteoblastic differentiation of human bone marrow-derived mesenchymal stem cells (hBMSCs). $TNF-{\alpha}$ dose-dependently promoted matrix mineralization of hBMSCs with a maximal stimulation at 2ng/ml. $TNF-{\alpha}$ increased expression of alkaline phosphatase, which plays a crucial role for the matrix deposition. The $TNF-{\alpha}-stimulated$ osteoblastic differentiation was not affected by $NF_kB$ inhibitors, BAY and SN50. However, a JNK-specific inhibitor, SP600125 completely abolished the $TNF-{\alpha}-stimulated$ matrix mineralization and expression of alkaline phosphatase. These results suggest that $TNF-{\alpha}$ enhances osteoblastic differentiation of hBMSCs through JNK-dependent pathway.

• Restorative Dentistry and Endodontics
• /
• v.24 no.1
• /
• pp.187-199
• /
• 1999

Bone remodeling is characterized by the continuing processes of osteoblast-mediated bone formation and osteoclast-mediated bone resorption. Bone metabolism is tightly regulated at the local level by networks of hormones, cytokines, and other factors. In pathological conditions of bone remodeling, including osteoporosis and periodontal diseases, inflammatory cytokines and local mediators are responsible for enhancement of osteoclast resorption and inhibition of repair at the sites of bone resorption. TNF-${\alpha}$ is a pleiotropic hormone with actions on the differentiation, growth, and functional activities of normal and malignant cells from numerous tissues. TNF-${\alpha}$ has been proposed as a local mediator of the control of bone turnover in situations of chronic inflammation, and it has been assumed that the local source of TNF-${\alpha}$ is the monocyte in the adjacent bone marrow or the local circulation. TNF-${\alpha}$ is a potent inducer of bone resorption. TNF-${\alpha}$ is known to induce the activation of apoptotic signaling pathway, which leads to the apoptosis of bone cells. We demonstrated that treatment of murine osteoblastic MC3T3E1 cells with TNF-${\alpha}$ decreases proliferation as well as alkaline phosphatase (ALP) activity in a dose depenent manner. In addition, TNF-${\alpha}$ increases osteoclast-like cell formation in $1{\alpha}$, 25(OH)2D3 or PGE2-treated bone marrow cell culture. When cells were cultured in TNF-${\alpha}$ free ${\alpha}$-MEM, this inhibitory effect of ALP activity was reversible up to 10 ng/ml TNF-${\alpha}$, in contrast, at the 20 ng/ml TNF-${\alpha}$, irreversible. In this concentration, TNF-${\alpha}$ may induce apoptosis in MC3T3E1 cells. In this study, TNF-${\alpha}$ induces apoptosis resulting in chromosomal DNA fragmentation, preceded by JNK/SAPKs and caspase-3 activation. Our present results show that JNK/SAPKs and caspase-3 are activated by TNF-${\alpha}$, suggesting that the JNK/SAPKs and caspase-3 participate in the bone resorption, associated with apoptosis.

• Maxillofacial Plastic and Reconstructive Surgery
• /
• v.35 no.6
• /
• pp.396-401
• /
• 2013

Chronic osteomyelitis is an infection and inflammation of the bone or bone marrow, causing ischemia in bone marrow due to lack of blood, nutrients, and oxygen supply to the bone marrow, eventually leading to necrosis of bone marrow. A current method for treatment of chronic osteomyelitis is administration of systemic antibiotics followed by removal of the infected bone and tissues. Because infected tissue of chronic osteomyelitis is surrounded by avascular necrotic bone, supply of blood and antibiotics to the infected area is diminished. For effective treatment, high plasma concentrations of antibiotics should be provided for a prolonged period. However, long term high serum level of antibiotics may result in undesirable adverse effects. For delivery of a sufficient concentration of antibiotic to the infected area while avoiding the adverse effect, implantation of a local antibiotic delivery system is suggested. One of the implantation systems that has been utilized is antibiotic impregnated polymethyl methacrylate.

• Clinics in Shoulder and Elbow
• /
• v.26 no.2
• /
• pp.191-204
• /
• 2023

Avascular necrosis (AVN) of the humeral head is a rare, yet detrimental complication. Left untreated, humeral head AVN frequently progresses to subchondral fracturing and articular collapse. Cases of late-stage humeral head AVN commonly require invasive procedures including humeral head resurfacing, hemiarthroplasty, and total shoulder arthroplasty (TSA) to improve clinical outcomes. However, in cases of early-stage AVN, core decompression of the humeral head is a viable and efficacious short-term treatment option for patients with pre-collapse AVN of the humeral head to improve clinical outcomes and prevent disease progression. Several techniques have been described, however, a percutaneous, arthroscopic-assisted technique may allow for accurate staging and concomitant treatment of intraarticular pathology during surgery, although further long-term clinical studies are necessary to assess its overall outcomes compared with standard techniques. Biologic adjunctive treatments, including synthetic bone grafting, autologous mesenchymal stem cell/bone marrow grafts, and bone allografts are viable options for reducing the progression of AVN to further collapse in the short term, although long-term follow-up with sufficient study power is lacking in current clinical studies. Further long-term outcome studies are required to determine the longevity of core decompression as a conservative measure for early-stage AVN of the humeral head.

• BMB Reports
• /
• v.57 no.5
• /
• pp.238-243
• /
• 2024

Bone marrow-derived mesenchymal stem cells (BM-MSCs) can differentiate into endothelial cells in an inflammatory microenvironment. However, the regulatory mechanisms underlying this process are not entirely understood. Here, we found that TIE2 in BM-MSCs was upregulated at the transcriptional level after stimulation with tumor necrosis factor-alpha (TNFα), a major pro-inflammatory cytokine. Additionally, the STAT-binding sequence within the proximal region of TIE2 was necessary for TNFα-induced TIE2 promoter activation. TIE2 and STAT3 knockdown reduced TNFα-induced endothelial tube formation in BM-MSCs. Among the major TNFα-activated MAP kinases (ERK1/2, JNK1/2, and p38 MAPK) in BM-MSCs, only inhibition of the p38 kinase abrogated TNFα-induced TIE2 upregulation by inhibiting the JAK-STAT signaling pathway. These findings suggest that p38 MAP contributes to the endothelial differentiation of BM-MSCs by activating the JAK-STAT-TIE2 signaling axis in the inflammatory microenvironment.

• Asian Pacific Journal of Cancer Prevention
• /
• v.17 no.12
• /
• pp.5273-5280
• /
• 2016

Objective: To evaluate stromal cells of the bone marrow microenvironment (BMM) in bone marrow trephine biopsy (BMTB) specimens, with a focus on fibronectin, tumor necrosis factor- alpha (TNF-${\alpha}$) and L-selectin in Non-Hodgkin's lymphoma (NHL) patients, before and after therapy. Materials and Methods: A total of 80 de novo NHL patients, 64 with B-cell lymphomas 80%, (follicular cell lymphoma (FCL) in 32, chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) in 12, and diffuse large cell lymphoma in 20) and 16 with T-cell lymphomas (20%) all diagnosed as T-Lymphoblastic lymphomas, were evaluated before and after therapy. For comparison, 25 age and sex matched BM donors, were included as a control group. BMTB material and BM aspirates were taken for morphological assessment of stromal cells, the plasma of these samples being examined for $TNF{\alpha}$ and L-selectin by ELISA, and fibronectin by radial immunodiffusion (RID). Results: BM stromal cells comprising reticular macrophages and fibroblasts were elevated in 53.3% of NHL cases at diagnosis, while BM fibronectin levels were decreased and BM $TNF{\alpha}$ and L-selectin were higher than in controls (p<0.05). In NHL cases, elevated values of BM $TNF{\alpha}$ and BM L-selectin were associated with signs of aggressive disease, including >1 extra nodal sites, detectable B symptoms, high grade, BM and CNS invasion, and a high International prognostic index (IPI) (p<0.05). Conclusion: BMM components, $TNF{\alpha}$, L-selectin and fibronectin, in NHL can be useful in evaluating disease activity, extent and response to treatment and as prognostic markers according to the IPI.