RRC ID 73468
Author Hatori T, Maeda T, Suzuki A, Takahashi K, Kato Y.
Title SPARC is a decoy counterpart for c‑Fos and is associated with osteoblastic differentiation of bone marrow stromal cells by inhibiting adipogenesis.
Journal Mol Med Rep
Abstract Secreted protein acidic and rich in cysteine (SPARC), also called basement‑membrane protein 40 or osteonectin, is a matricellular protein that is abundant not only in bone tissue as a non‑collagenous protein but is also ubiquitously expressed in non‑calcified tissue. SPARC is located intracellularly and disruption of the Sparc gene has been reported to reduce bone formation and increase fat tissue; however, the mechanism by which SPARC inhibits adipogenesis remains unclear. The present study evaluated the intracellular function of SPARC in adipogenesis using the bone marrow stromal cell line ST2. When ST2 cells with low SPARC production were cloned, intrinsic activator protein‑1 (AP‑1) activity was markedly higher, mineralized nodule formation was significantly lower and lipid accumulation was significantly increased compared with in the parental ST2 cells. Forced expression of secreted SPARC with the signal peptide‑coding sequences of wild‑type Sparc or preprotrypsin in SPARC‑low ST2 cells significantly reduced AP‑1 transcription activity; however, these reductions were not observed in the absence of signal peptide sequences. Recombinant SPARC, produced using Brevibacillus brevis, specifically bound to c‑Fos but not c‑Jun and inhibited the binding of c‑Fos/c‑Jun to a TPA‑response element sequence. These data suggested that SPARC was incorporated into the cells from the extracellular spaces and serves an intracellular role as a decoy counterpart for c‑Fos, as well as being associated with osteoblastogenesis through the inhibition of adipogenesis. These findings may provide new insights into regenerative medicine.
Volume 27(2)
Published 2023-2-1
DOI 10.3892/mmr.2023.12937
PII 50
PMID 36633137
MeSH Adipogenesis / genetics Cell Differentiation / genetics Interleukin-1 Receptor-Like 1 Protein / metabolism Mesenchymal Stem Cells* / metabolism Osteonectin* / genetics Osteonectin* / metabolism Protein Sorting Signals Proto-Oncogene Proteins c-fos / genetics Proto-Oncogene Proteins c-fos / metabolism Transcription Factor AP-1 / genetics Transcription Factor AP-1 / metabolism
Human and Animal Cells ST2(RCB0224)