Kielin/chordin‐like protein enhances induction of osteoblast differentiation by Bone Morphogenetic Protein‐2

Abstract

Bone morphogenetic proteins (BMPs) play a key role in embryonic differentiation for osteoblast and bone formation. Kielin/chordin-like protein (Kcp) is known to enhance the effects of BMP signaling. Here, we present ALP activity, gene expression, and calcification data demonstrating that Kcp affects the differentiation of C2C12 myoblasts into osteoblasts. We report that the presence of Kcp enhances the ability of BMP-2 to induce the differentiation of C2C12 myoblasts into osteoblasts. Additionally, BMP-2-mediated stimulation of phosphorylated Smad1/5 was apparently enhanced in the presence of Kcp. The present findings may contribute to progression toward the clinical use of BMPs for treatment of bone fracture, osteoarthritis, and other similar conditions.Bone morphogenetic proteins (BMPs), secreted signal transmitters that belong to the TGF-b superfamily, are generally known to have effects causing induction of differentiation of stem cells into osteoblasts [1], with several types and various functions reported [2]. For example, BMP-1 promotes collagenous proliferation and cartilage formation [3], while BMP-4 promotes neural plate formation in the embryologic phase, which later develops into the central nervous system [4]. Furthermore, BMP-6 plays an extremely important role in iron homeostasis for formation of hepcidin [5] and BMP-15 promotes follicle formation in the ovaries [6].

Kielin/chordin‐like protein deficiency aggravates pressure overload‐induced cardiac dysfunction and remodeling via P53/P21/CCNB1 signaling in mice

“…Kielin/chordin-like protein (KCP) is a secretory protein with 18 cysteine-rich domains. 4 Previous studies have shown that KCP is an enhancer of bone morphogenetic proteins (BMP) signaling and suppressor of transforming growth factor β (TGF-β) signaling, 4 which are both involved in the regulation of fibrosis and cardiac remodeling. 5 It has been reported that KCP promotes BMP7 binding to its receptor, increasing the phosphorylation of intracellular Smad1, thereby ameliorating renal fibrosis.…”