Cartducin, a paralog of Acrp30/adiponectin, is induced during chondrogenic differentiation and promotes proliferation of chondrogenic precursors and chondrocytes

Abstract

We previously reported that CORS26 gene, isolated from C3H10T1/2 cells treated with transforming growth factor-beta1, was predominantly expressed in cartilage. Because the gene product is a kind of secretory protein produced by cartilage tissue, we named it "cartducin". Cartducin shares a similar modular organization to adipocyte-derived hormone, adiponectin. In this study, we investigated cartducin function during chondrogenesis and cartilage development. In situ hybridization analysis showed that cartducin transcripts were restricted to the proliferating chondrocytes in the growth plate cartilage. Whole-mount in situ hybridization revealed that the first significant induction of cartducin expression occurred in the sclerotome, which contains a chondrogenic cell lineage between days 9.5 and 10.5 postcoitus (p.c.) during mouse embryogenesis. Chondrogenic differentiation by combined treatment with bone morphogenetic protein-2 and insulin induced cartducin expression along with type II and IX collagen expression in chondrogenic progenitor N1511 cells. To elucidate the direct action of cartducin on the cells, recombinant cartducin protein was expressed in and purified from Escherichia coli. The recombinant cartducin potentially forms homo-oligomers and promoted the proliferation of chondrogenic progenitor N1511 cells, and chondrocytic HCS-2/8 cells in a dose-dependent manner. On the other hand, cartducin did not affect the production of sulfated glycosaminoglycan (sGAG) in these cells. These findings indicate that cartducin is a novel growth factor and plays important roles in regulating both chondrogenesis and cartilage development by its direct stimulatory action on the proliferation of chondrogenic precursors and chondrocytes.

C1q/TNF-related Protein-12 (CTRP12), a Novel Adipokine That Improves Insulin Sensitivity and Glycemic Control in Mouse Models of Obesity and Diabetes

“…The defining feature of CTRPs is the presence of the signature "C1q/TNF-like" globular domain located at the C terminus, which is homologous to the immune complement C1q and structurally resembles that of TNF-␣ (9). Functional studies thus far have indicated significant roles for CTRPs in the endocrine (4 -8, 10, 11), immune (12), vascular (13,14), skeletal (15), and sensory systems (16 -18).…”

C1q Tumor Necrosis Factor α-related Protein Isoform 5 Is Increased in Mitochondrial DNA-depleted Myocytes and Activates AMP-activated Protein Kinase

“…C1QTNF1, which is expressed by vascular smooth muscle cells, inhibits collagen-induced platelet aggregation (9) and activates Akt and MAPK (10). C1QTNF3 is expressed by chondrocytes, and recombinant C1QTNF3 stimulates cartilage development by activating extracellular signalregulated kinase (ERK) and Akt signaling pathway (11,12). Recently, it was reported that C1QTNF2 induces the phosphorylation of AMPK in C2C12 myocytes, resulting in increased glycogen accumulation and fatty acid oxidation (6).…”

COLLAGENOUS REPEAT-CONTAINING SEQUENCE OF 26 kDa PROTEIN - A NEWLY DISCOVERED ADIPOKINE - SENSU LATO - A MINIREVIEW

“…Whereas adiponectin is exclusively expressed by adipocytes, CORS-26 mRNA is also detected in cartilage, kidney, colon, small intestine, placenta, lung, spleen, fibroblasts, human monocytic and dendritic cells 5,6 . In addition, strong CORS-26 mRNA expression has been found in osteosarcoma, chondroblastoma and giant cell tumors 2,3,6 .…”

“…CORS-26 has been shown to be a novel growth factor that plays an important role in regulating both chondrogenesis and cartilage development (CORS-26 gene is predominantly expressed in growth plate cartilage) 5,8 . Skeletal development requires condensation of multipotential mesenchymal cells in order to differentiate into various cell types.…”

“…The human homolog of the mouse CORS-26 gene has also been identified and mapped to the chromosome locus 5p13.2-13.1 which is close to the locus of the growth hormone receptor (GHR) gene (5p13. [1][2][3][4][5][6][7][8][9][10][11][12] 2,3,5 .…”