title: Supplementation of strontium to a chondrogenic medium promotes chondrogenic differentiation of human dedifferentiated fat cells.
abstract: Dedifferentiated fat cells (DFAT cells) isolated from adipose tissue have been demonstrated to differentiate into chondrogenic cells in vitro. Nevertheless, an efficient method to facilitate its chondrogenic differentiation is still unexplored, hampering the extensive application of these cells in cartilage regeneration therapies. Here we provide the evidence that supplementation of strontium ions (Sr) in a chondrogenic medium (CM) significantly promotes early chondrogenic differentiation of DFAT cells. Human DFAT cells and the mesenchymal stem cell line (RCB2153) were subjected to the CM supplemented with/without Sr. After 14 days, alcian blue staining intensity significantly increased in DFAT cells, but not in RCB2153, subjected to CM with Sr. mRNA expression analysis revealed that the CM with 1.5 mM Sr increased the expression of chondrogenic marker, collagen type 2 alpha 1, whereas there was no significant change in osteogenic markers, collagen type 1 alpha 1, runt-related transcription factor 2, and osteocalcin, and hypertrophic chondrogenic marker, collagen type 10 alpha 1. Inhibitors for extracellular signal-regulated kinase 1/2 (ERK1/2), Akt, and calcium-sensing receptor (CaSR) pathways significantly diminished the alcian blue staining intensity, providing the first evidence that these signal pathways are associated with chondrogenic differentiation of DFAT cells. CaSR and ERK1/2 pathways independently induced Sr-mediated early chondrogenic differentiation. These results suggest that Sr supplementation into the CM may provide a powerful platform for preparing chondrogenically differentiated DFAT cells for cartilage regeneration.
authors: 1 Department of Orthodontics, Osaka Dental University , Osaka, Japan .
authors: Naoya
authors: N
authors: Okita
authors: Yoshitomo
authors: Y
authors: Honda
authors: Naotaka
authors: N
authors: Kishimoto
authors: Wen
authors: W
authors: Liao
authors: Eiko
authors: E
authors: Azumi
authors: Yoshiya
authors: Y
authors: Hashimoto
authors: Naoyuki
authors: N
authors: Matsumoto
mesh_terms: D017667:Adipocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D015153:Blotting, Western; D054337:Cell Dedifferentiation / Q000187:drug effects* / Q000235:genetics; D002454:Cell Differentiation / Q000187:drug effects* / Q000235:genetics; D002460:Cell Line; D019902:Chondrocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D020219:Chondrogenesis / Q000187:drug effects* / Q000235:genetics; D003470:Culture Media / Q000494:pharmacology*; D005260:Female; D005455:Fluorescent Antibody Technique; D020869:Gene Expression Profiling; D006801:Humans; D006984:Hypertrophy; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D010006:Osteoblasts / Q000187:drug effects / Q000378:metabolism; D010012:Osteogenesis / Q000187:drug effects / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D013324:Strontium / Q000494:pharmacology*
chemical_list: D015415:Biomarkers; D003470:Culture Media; D012333:RNA, Messenger; D013324:Strontium