SPARC is a decoy counterpart for c‑Fos and is associated with osteoblastic differentiation of bone marrow stromal cells by inhibiting adipogenesis

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.

ROS impairs tumor vasculature normalization through an endocytosis effect of caveolae on extracellular SPARC

“…SPARC is an extracellular calcium-binding glycoprotein that participates in a variety of cellular processes, including promoting inflammatory cell aging [ 38 ], regulating stromal cell differentiation [ 39 ], and increasing tumor cell invasion [ 40 ]. SPARC is also engaged in pericyte recruitment and neo-angiogenesis [ 17 ].…”

FOS Inhibits the Differentiation of Intramuscular Adipocytes in Goats

“…It has been reported that FOS proteins are highly expressed in NASH mice, and microRNA29c can regulate the course of NASH by targeting FOS proteins [37]. The specific binding from SPARC to C-FOS leads to a decrease in AP-1 activity, which inhibits adipogenesis but promotes osteoclast differentiation [38]. These previous findings are inconsistent with the results of this study, and we speculated that the various roles played by FOS in adipogenesis may be attributed to species variations and inconsistent mechanisms of action.…”

Sword Bean (Canavalia gladiata) Pods Induce Differentiation in MC3T3-E1 Osteoblast Cells by Activating the BMP2/SMAD/RUNX2 Pathway

“…It is associated with the expression of OCN, OPN, and growth factors involved in bone formation. SPARC commits cells to the osteoblast lineage by inhibiting their differentiation into adipocytes [10]. Several studies have suggested that activation of BMP2/SMAD and RUNX2 signals is involved in osteoblast differentiation [11,12].…”