Gene array profile identifies collagen type XV as a novel human osteoblast-secreted matrix protein.
Bone marrow stromal cells (MSCs) and osteoblasts are the two main non-haematopoietic cellular components of human bone tissue. To identify novel osteoblast-related molecules, we performed a gene expression profiling analysis comparing MSCs and osteoblasts isolated from the same donors. Genes differentially overexpressed in osteoblasts were mainly related to the negative control of cell proliferation, pro-apoptotic processes, protein metabolism and bone remodelling. Notably, we also identified the collagen XV (COL15A1) gene as the most up-regulated gene in osteoblasts compared with MSCs, previously described as being expressed in the basement membrane in other cell types. The expression of collagen type XV was confirmed at the protein level on isolated osteoblasts and we demonstrated that it significantly increases during the osteogenic differentiation of MSCs in vitro and that free ionised extracellular calcium significantly down-modulates its expression. Moreover, light and electron microscopy showed that collagen type XV is expressed in bone tissue biopsies mainly by working osteoblasts forming new bone tissue or lining bone trabeculae. To our knowledge, these data represent the first evidence of the expression of collagen type XV in human osteoblasts, a calcium-regulated protein which correlates to a specific functional state of these cells.
Lisignoli
Gina
G
Laboratorio di Immunologia e Genetica, Istituto Ortopedico Rizzoli, Bologna, Italy. immunologia@ior.it
Codeluppi
Katia
K
Todoerti
Katia
K
Manferdini
Cristina
C
Piacentini
Anna
A
Zini
Nicoletta
N
Grassi
Francesco
F
Cattini
Luca
L
Piva
Roberta
R
Rizzoli
Vittorio
V
Facchini
Andrea
A
Giuliani
Nicola
N
Neri
Antonino
A
D000368:Aged; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology; D049109:Cell Proliferation; D002478:Cells, Cultured; D003094:Collagen / Q000235:genetics / Q000378:metabolism*; D005109:Extracellular Matrix / Q000737:chemistry / Q000378:metabolism*; D020869:Gene Expression Profiling; D006801:Humans; D046228:Microarray Analysis; D008875:Middle Aged; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism*; D010012:Osteogenesis / Q000502:physiology; D010641:Phenotype; D017154:Stromal Cells / Q000166:cytology / Q000378:metabolism
C085811:COL15A1 protein, human; D003094:Collagen; D002118:Calcium