Expression of Glucagon-Like Peptide 1 Receptor during Osteogenic Differentiation of Adipose-Derived Stem Cells

BACKGROUND: Glucagon-like peptide 1 (GLP-1), an incretin hormone well known for its glucose-lowering effect, was recently reported to exert an anabolic effect on bone. Although the exact mechanism is not known, it likely involves the GLP-1 receptor (GLP-1R), which is expressed in some osteoblastic cell lines. Adipose-derived stem cells (ADSCs) have mesenchymal stem cell-specific characteristics, including osteoblastic differentiation potential. We evaluated the expression of GLP-1R during osteogenic differentiation of ADSCs. METHODS: ADSCs were isolated from subcutaneous adipose tissue obtained from three male donors during plastic surgery and were subjected to osteogenic induction. Mineralization was assessed by Alizarin Red staining on day 21. Expression of alkaline phosphatase (ALP), osteocalcin (OC), and GLP-1R was measured by real-time polymerase chain reaction in triplicate for each patient on days 0, 7, 14, and 21. Target mRNA expression levels were normalized to that of beta-actin. RESULTS: ADSCs were fibroblast-like in morphology, adhered to plastic, and had multipotent differentiation potential, as assessed using specific antigen markers. The osteogenic markers ALP and OC were notably upregulated at 21 days. Osteogenic differentiation resulted in a time-dependent increase in the expression of GLP-1R (P=0.013). CONCLUSION: We demonstrated upregulation of GLP-1R gene expression during osteogenic differentiation of ADSCs. This finding suggests that GLP-1 may induce osteogenic differentiation in bone tissue.

Increased Interleukin-17 Expression in Patients with Idiopathic Inflammatory Myopathies / 대한류마티스학회지

OBJECTIVE: Idiopathic inflammatory myopathies (IIMs) are systemic autoimmune diseases characterized by infiltration of T lymphocytes, monocytes, and macrophages in muscle tissues. Interleukin-17 (IL-17), a Th17 cytokine, has potent pro-inflammatory actions and plays a role in autoimmune diseases. We investigated the expression of IL-17 in muscle tissues of patients with IIMs. METHODS: We measured the IL-17 mRNA level of muscle tissues from 14 patients with IIMs (9 patients with dermatomyositis and 5 patients with polymyositis) by real-time RT-PCR and compared with controls. We also performed an immunohistochemical stain to detect IL-17 expression. RESULTS: The expressions of IL-17 were significantly enhanced in IIMs than controls. In immunohistochemistry, IL-17 was expressed in perimysial, endomysial and perivascular infiltrating inflammatory cells. CONCLUSION: These results suggest that IL-17 plays a role in the immunopathogenesis of IIMs.

The Expression of Toll-like Receptors in Idiopathic Inflammatory Myopathies / 대한류마티스학회지

Objective: To investigate the expression of toll-like receptor (TLR)-2, 4 and 9 in idiopathic inflammatory myopathies (IIMs). Methods: The expression of TLR-2, 4 and 9 was measured by real-time RT-PCR and immunohistochemical stain (IHS) from muscle tissues in patients with IIMs and controls. Results: The expression levels of TLR-2, 4 and 9 in IIMs were significantly higher than controls. TLR-2, 4 and 9 were mainly expressed on sarcolemma of muscle fibers, perimysial vascular endothelium and infiltrating inflammatory cells in dermatomyositis, whereas, they were mainly expressed on sarcolemma of muscle fibers, destructed muscle fibers, and enodmysial infiltrating inflammatory cells in polymyositis. Conclusion: TLR-2, 4 and 9 were highly expressed in muscle tissue of IIMs. These results suggest that TLR-2, 4 and 9 play a role in pathogenesis of IIMs.

Synovial RANKL/OPG mRNA Ratio and Effect of IL-17 in Experimental Rheumatoid Arthritis Model / 대한류마티스학회지

OBJECTIVE: To investigate the synovial mRNA expression of receptor activator of NFkappaB (RANK), RANK ligand (RANKL), osteoprotegerin (OPG) and RANKL/OPG mRNA expression ratio, and to evaluate the effects of IL-17 in experimental rheumatoid arthritis (RA) model. METHODS: After induction of collagen-induced arthritis (CIA) by type II collagen in DBA1 mice, mice were anesthetized at day 28 and a small aperture in the skin of the knee was performed. Mice, in which arthritis of knee was present, were selected and divided into 3 groups, and phosphate-buffered saline (PBS group), IL-17 (IL-17 group) or anti-IL-17 monoclonal antibody (anti-IL-17 group) was injected to both knee joint at day 28 and 32. At day 35, mice were sacrificed and synovium of knee joints were isolated. Synovial mRNA expression of RANKL, RANK and OPG was assessed by real-time RT-PCR and immunohistochemical stain. RESULTS: Synovial RANKL and RANK mRNA expressions were significantly different among IL-17, PBS, anti-IL-17 and normal group (IL-17>PBS>anti-IL-17>normal group), and synovial OPG mRNA expressions in PBS, IL-17 and anti-IL-17 group were significantly high than those in normal group, however, there was no significant difference among IL-17, PBS and anti-IL-17 group. RANKL/OPG mRNA ratio was significantly different among these groups (IL-17>PBS>anti-IL-17>normal group). In immunohistochemical stain, RANKL, RANK and OPG-positive cells were expressed at synovium. CONCLUSION: Synovial RANKL/OPG mRNA ratio was enhanced in CIA, and IL-17 induced higher RANKL/OPG ratio in the synovium of CIA, which was blocked by anti-IL-17 antibody. These results suggest that RANKL/OPG mRNA ratio play an important roles on bone destruction, and IL-17 may be actively involved in bone destruction by enhancing RANKL/OPG ratio in CIA model.

The Expression of Toll-like Receptors in Collagen-induced Arthritis / 대한류마티스학회지

OBJECTIVE: To evaluate the expression of Toll-like receptor (TLR) 2, 4 and 9 and investigate the effects of IL-17 on the expression of TLRs in experimental rheumatoid arthritis (RA) model. METHODS: After induction of collagen-induced arthritis (CIA) by type II collagen in DBA1 mice, phosphate-buffered saline (PBS, PBS group) or IL-17 (IL-17 group) was injected to both knee joint at day 28 and 32. At day 35, mice were sacrificed and knee joints were isolated. Synovial mRNA expressions of TLR-2, 4 and 9 determined by real-time RT-PCR were compared among normal DBA1 mice (normal group), PBS and IL-17 group. RESULTS: Synovial TLR-2, 4, and 9 mRNA expressions of IL-17 and PBS group were significantly higher than normal group, and those of IL-17 group were higher than PBS group. CONCLUSION: Synovial TLR-2, 4 and 9 expression was enhanced in CIA and up-regulated by local overexpression of IL-17. These results suggest that TLRs play a roles on CIA and IL-17 induced aggravation of arthritis in CIA.

A Case of Pulmonary Hypertension with Pulmonary Arteritis Diagnosed as Takayasu's Arteritis Type IV

Takayasu's arteritis is a chronic inflammatory disease of unknown etiology involving the thoracic and abdominal aorta and its major branches. In some cases other vessel such as renal arteries, coronary arteries, and even pulmonary arteries may be involved. Total aortography is very important, because the clinical features are determined by the extent and severity of the specific artery involved in the occlusive phase of the disease. We report a case of Takayasu's arteritis type IV in a 38 year man with pulmonary arterial involvement and pulmo-nary hypertension.

Clinical significance of CA125 level in tuberculous pneumonia / 결핵

BACKGROUND: In case of tuberculous pneumonia, differentiation from bacterial lobar pneumonia is sometimes very difficult because clinical symptoms, signs and radiological images are very similar. So we investigated the usefulness of CA125, which is known to increase in tuberculous diseases, in differential diagnosis between tuberculous pneumonia (TBPN) and community acquired bacterial lobar pneumonia (LP). METHODS: Serum CA125 level was measured in 20 patients with TBPN (female 12 male 8: mean age 36.1 years) and 14 patients with LP (female 5 male 9: mean age 45.1 years) by radioimmunoassay (Centocor(R) CA125 RIA kit). RESULTS: 1) The serum CA125 level in TBPN (333.7 283.5 u/ml) was higher than in LP (60.9 66.2 u/ml). (P 0.05) 4) Following up of serum CA125 level after initiation of antituberculosis treatment showed rapid decline and approach to near normal range in 6 months. CONCLUSION: High serum CA125 level (> 195 u/ml) was useful in differential diagnosis of TBPN from LP.