Anti-TNFRSF11B monoclonal antibody, clone 6H3

Objective: Prior studies have shown that receptor activator of nuclear factor-B ligand (RANKL) and osteoprotegerin (OPG) have an essential role in bone remodeling and osteoporosis. This study aimed to investigate the association between RANKL (TNFSF11) and OPG (TNFRSF11B) genes' polymorphisms with low bone mineral density (BMD) in Indonesian postmenopausal women. Materials and Methods: Sixty postmenopausal women aged between 50-65 years were eligible. The BMD was measured by using dual-energy X-ray absorptiometry. The genotypes of TNFSF11 and TNFRSF11B were obtained by polymerase chain reaction-restriction fragment length polymorphisms and DNA sequencing methods. Three single nucleotide polymorphisms (SNPs) from TNFSF11 (-290C>T, -643C>T, -693G>C) and from TNFRSF11B (163A>G, 950T>C, 1181G>C) were selected. The association between alleles distribution and BMD was computed using chi-square or Fischer's exact test. Multiple logistic regression was used to analyze between all SNPs and BMD at bone sites. Significance was set at p<0.05. Results: Most subjects had lower BMD (83.3%). Characteristics of subjects between healthy and low BMD were comparable (all p>0.05). The distribution of genotypes and alleles in TNSSF11 and TNFRSF11B between healthy and low BMD were not significantly different (all p>0.05). There was no association between SNPs of TNFSF11 and TNFRSF11B with BMD at all bone sites (all p>0.05). Conclusion: The present study suggests that TNFSF11 and TNFRSF11B gene polymorphisms are not associated with BMD in Indonesian postmenopausal women aged between 50-65 years old.

Background: Chronic pancreatitis has surgical options including total pancreatectomy to control pain. To avoid surgical diabetes, the explanted pancreas can have islets harvested and transplanted. Immediately following total pancreatectomy with islet autotransplantation (TP-IAT), many islet cells die due to isolation and transplantation stresses. The percentage of patients remaining insulin free after TP-IAT is therefore low. We determined whether cotransplantation of adipose-derived mesenchymal stem cells (ASCs) from chronic pancreatitis patients (CP-ASCs) would protect islets after transplantation. Methods: In a marginal mass islet transplantation model, islets from C57BL/6 mice were cotransplanted with CPASCs into syngeneic streptozotocin-treated diabetic mice. Treatment response was defined by the percentage of recipients reaching normoglycemia, and by the area under the curve for glucose and c-peptide in a glucose tolerance test. Macrophage infiltration, beta-cell apoptosis, and islet graft vasculature were measured in transplanted islet grafts by immunohistochemistry. mRNA expression profiling of 84 apoptosis-related genes in islet grafts transplanted alone or with CP-ASCs was measured by the RT2 Profiler((TM)) Apoptosis PCR Array. The impact of insulin like growth factor 1 (IGF 1) on islet apoptosis was determined in islets stimulated with cytokines (IL 1 beta and IFN gamma)in the presence and absence of CP-ASC conditioned medium. Results: CP-ASC-treated mice were more often normoglycemic compared to mice receiving islets alone. ASC cotransplantation reduced macrophage infiltration, beta-cell death, suppressed expression of TNF-alpha and Bcl-2 modifying factor (BMF), and upregulated expressions of IGF-1 and TNF Receptor Superfamily Member 11b (TNFRSF11B) in islet grafts. Islets cultured in conditioned medium from CP-ASCs showed reduced cell death. This protective effect was diminished when IGF-1 was blocked in the conditioned medium by the anti IGF-1 antibody. Conclusion: Cotransplantation of islets with ASCs from the adipose of chronic pancreatitis patients improved islet survival and islet function after transplantation. The effects are in part mediated by paracrine secretion of IGF-1, suppression of inflammation, and promotion of angiogenesis. ASCs from chronic pancreatitis patients have the potential to be used as a synergistic therapy to enhance the efficacy of islet transplantation following pancreatectomy.