Tenascin-W inhibits proliferation and differentiation of preosteoblasts during endochondral bone formation.
We identified a cDNA encoding mouse Tenascin-W (TN-W) upregulated by bone morphogenetic protein (Bmp)2 in ATDC5 osteo-chondroprogenitors. In adult mice, TN-W was markedly expressed in bone. In mouse embryos, during endochondral bone formation TN-W was localized in perichondrium/periosteum, but not in trabecular and cortical bones. During bone fracture repair, cells in the newly formed perichondrium/periosteum surrounding the cartilaginous callus expressed TN-W. Furthermore, TN-W was detectable in perichondrium/periosteum of Runx2-null and Osterix-null embryos, indicating that TN-W is expressed in preosteoblasts. In CFU-F and -O cells, TN-W had no effect on initiation of osteogenesis of bone marrow cells, and in MC3T3-E1 osteoblastic cells TN-W inhibited cell proliferation and Col1a1 expression. In addition, TN-W suppressed canonical Wnt signaling which stimulates osteoblastic differentiation. Our results indicate that TN-W is a novel marker of preosteoblasts in early stage of osteogenesis, and that TN-W inhibits cell proliferation and differentiation of preosteoblasts mediated by canonical Wnt signaling.
Kimura
Hiroaki
H
Department of Orthopaedics, Kyoto University, Kyoto 606-8507, Japan.
Akiyama
Haruhiko
H
Nakamura
Takashi
T
de Crombrugghe
Benoit
B
D000818:Animals; D001846:Bone Development / Q000187:drug effects / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology; D049109:Cell Proliferation; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000502:physiology*; D051379:Mice; D008813:Mice, Inbred ICR; D010006:Osteoblasts / Q000166:cytology* / Q000502:physiology*; D010012:Osteogenesis / Q000502:physiology; D019063:Tenascin / Q000378:metabolism*; D051153:Wnt Proteins / Q000378:metabolism*; D029961:Zebrafish Proteins / Q000378:metabolism*
D019063:Tenascin; D051153:Wnt Proteins; D029961:Zebrafish Proteins; C112411:tnn protein, zebrafish