Cooperative actions of hepatocyte growth factor and 1,25-dihydroxyvitamin D3 in osteoblastic differentiation of human vertebral bone marrow stromal cells

• Published in: Bone (New York, N.Y.) Vol. 31; no. 2; pp. 269 - 275
• Main Authors: D'IPPOLITO, G, SCHILLER, P. C, PEREZ-STABLE, C, BALKAN, W, ROOS, B. A, HOWARD, G. A
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Science 01.08.2002
• Subjects: Adult; Alkaline Phosphatase - metabolism; Biological and medical sciences; Bone Marrow Cells - cytology; Bone Marrow Cells - drug effects; Bone Marrow Cells - enzymology; Cell Count - methods; Cell Differentiation - drug effects; Cell Differentiation - physiology; Cells, Cultured; Cholecalciferol - pharmacology; Female; Fundamental and applied biological sciences. Psychology; Hepatocyte Growth Factor - pharmacology; Humans; Male; Osteoblasts - cytology; Osteoblasts - drug effects; Osteoblasts - enzymology; Skeleton and joints; Spine - cytology; Spine - drug effects; Spine - enzymology; Stromal Cells - cytology; Stromal Cells - drug effects; Stromal Cells - enzymology; Vertebrates: osteoarticular system, musculoskeletal system; Human; Cell culture; Cholecalciferol(1,25-dihydroxy); Hepatocyte growth factor; Stem cell; Vertebra; Cell differentiation; In vitro; Biological activity; Osteoarticular system; Vitamin D; Bone marrow; Osteoblast; Bone; Osteogenesis; Growth factor
• ISSN: 8756-3282; 1873-2763
• DOI: 10.1016/s8756-3282(02)00820-7

Bone formation and remodeling require continuous generation of osteoprogenitor cells from bone marrow stromal cells (MSC), which generate and respond to a variety of growth factors with putative roles in hematopoiesis and mesenchymal differentiation. In this study we examine the interaction of two such factors on the maturation of skeletal components. We previously reported that these factors, hepatocyte growth factor (HGF) and 1,25-dihydroxyvitamin D(3) (vitD(3)), act together to increase alkaline phosphatase in chondroblasts. We now describe the cooperative effect of these agents on MSC isolated and cultured from human vertebral bone marrow. MSC (passages 3-9) isolated from bone marrow cells of human vertebrae (T1-L5) from 22-36-year-old normal donors were first expanded in vitro and then plated in the presence or absence of 10 ng/mL HGF and/or 10 nmol/L vitD(3), for 7-18 days. HGF treatment increased cell proliferation 2.5-fold, with no effect on alkaline phosphatase activity. Whereas vitD(3) treatment inhibited cell growth by 50%, alkaline phosphatase activity was stimulated eightfold, although no mineralization was observed. HGF together with vitD(3) increased cell proliferation 1.5-fold and alkaline phosphatase activity 13-fold over untreated control. Moreover, mineralization was detected only with this combination. Our findings provide evidence that HGF in concert with vitamin D may promote growth and differentiation of human MSC into osteogenic cells.