ABSTRACT
Bone homeostasis is regulated by constant remodeling through osteogenesis by osteoblasts and osteolysis by osteoclasts and osteoporosis can be provoked when this balance is broken. Present pharmaceutical treatments for osteoporosis have harmful side effects and thus, our goal was to develop therapeutics from intrisincally safe natural products. Fucoidan is a polysaccharide extracted from many species of brown seaweed, with valuable pharmaceutical activities. To intensify the effect of fucoidan on bone homeostasis, we hydrolyzed fucoidan using AMG, Pectinex and Viscozyme. Of these, fucoidan biotransformed by Pectinex (Fu/Pec) powerfully inhibited the induction of tartrate-resistant acid phosphatase (TRAP) activity in osteoclasts differentiated from bone marrow macrophages (BMMs) by the receptor for activation of nuclear factor-κB ligand (RANKL). To investigate potential of lower molecular weight fucoidan it was separated into >300 kDa, 50-300 kDa, and <50 kDa Fu/Pec fractions by ultrafiltration system. The effects of these fractions on TRAP and alkaline phosphatase (ALP) activities were then examined in differentiated osteoclasts and MC3T3-E1 osteoblasts, respectively. Interestingly, 50-300 kDa Fu/Pec suppressed RANKL-induced osteoclasts differentiation from BMMs but did not synergistically enhance osteoblasts differentiation induced by osteogenic agents. In addition, this fraction inhibited the expressions of NFATc1, TRAP, OSCAR, and RANK, which are all key transcriptional factors involved in osteoclast differentiation, and those of Src, c-Fos and Mitf, as determined by RT-PCR. In conclusion, enzymatically low-molecularized 50-300 kDa Fu/Pec suppressed TRAP by downregulating RANKL-related signaling, contributing to the inhibition of osteoclasts differentiation, and represented a potential means of inducing bone remodeling in the background of osteoporosis.
Subject(s)
Osteoclasts , Osteoporosis , Cell Differentiation , Humans , Ligands , NF-kappa B , NFATC Transcription Factors , Osteogenesis , Pharmaceutical Preparations , Polysaccharides , RANK LigandABSTRACT
beta-Catenin/Tcf and NF-kappaB pathways play an important role in biological functions. We determined the underlying mechanisms of differential interaction between two pathways in various human cancer cell lines. NF-kappaB positively regulated beta-catenin/Tcf pathways in human glioblastoma, whereas it has an opposite effect on beta-catenin/Tcf pathways in colon, liver, and breast cancer cells. Expression of lucine zipper tumor suppressor 2 (lzts2) was positively regulated by NF-kappaB activity in colon, liver, and breast cancer cells, whereas negatively regulated in glioma cells. Downregulation of lzts2 increased the beta-catenin/Tcf promoter activity and inhibited NF-kappaB-induced modulation of the nuclear translocation of beta-catenin. These data indicate that the differential crosstalk between beta-catenin/Tcf and NF-kappaB pathway in various cancer cells is resulted from the differences in the regulation of NF-kappaB-induced lzts2 expression.
Subject(s)
NF-kappa B/metabolism , Neoplasms/metabolism , Neoplasms/pathology , TCF Transcription Factors/metabolism , beta Catenin/metabolism , Cell Cycle Proteins/genetics , Cell Cycle Proteins/metabolism , Cell Line, Tumor , DNA-Binding Proteins/genetics , DNA-Binding Proteins/metabolism , Down-Regulation/drug effects , Gene Expression Regulation, Neoplastic/drug effects , Humans , Models, Biological , NF-kappa B/antagonists & inhibitors , Peptides/pharmacology , Signal Transduction/drug effects , Tumor Suppressor Proteins/genetics , Tumor Suppressor Proteins/metabolismABSTRACT
Synovial hemangioma of a knee joint has been reported as a rare cause of pain, hemarthrosis, and intermittent locking. This case report describes our experience in excising intra-articular hemangioma of the knee joint. Complete resection, after arthroscopic examination, was performed in a 59-year-old man. Six months after the surgery, no evidence of recurrence was seen.
