Mice lacking osteopontin show normal development and bone structure but display altered osteoclast formation in vitro.
We have used homologous recombination in embryonic stem cells to generate mice with a targeted disruption of the osteopontin (Opn, or Spp1, for secreted phosphoprotein 1) gene. Mice homozygous for this disruption fail to express osteopontin (OPN) as assessed at both the mRNA and protein level, although an N-terminal fragment of OPN is detectable at extremely low levels in the bones of -/- animals. The Opn -/- mice are fertile, their litter size is normal, and they develop normally. The bones and teeth of animals not expressing OPN are morphologically normal at the level of light and electron microscopy, and the skeletal structure of young animals is normal as assessed by radiography. Ultrastructurally, proteinaceous structures normally rich in OPN, such as cement lines, persist in the bones of the Opn-/- animals. Osteoclastogenesis was assessed in vitro in cocultures with a feeder layer of calvarial osteoblast cells from wild-type mice. Spleen cells from Opn-/- mice cells formed osteoclasts 3- to 13-fold more frequently than did control Opn+/+ cells, while the extent of osteoclast development from Opn -/- bone marrow cells was about 2- to 4-fold more than from the corresponding wild-type cells. Osteoclast development occurred when Opn-/- spleen cells were differentiated in the presence of Opn-/-osteoblasts, indicating that endogenous OPN is not required for this process. These results suggest that OPN is not essential for normal mouse development and osteogenesis, but can modulate osteoclast differentiation.
Rittling
S R
SR
Department of Cell Biology and Neuroscience, Rutgers University, Piscataway, New Jersey, USA.
Matsumoto
H N
HN
McKee
M D
MD
Nanci
A
A
An
X R
XR
Novick
K E
KE
Kowalski
A J
AJ
Noda
M
M
Denhardt
D T
DT
D000818:Animals; D015519:Bone Density; D001846:Bone Development / Q000502:physiology*; D001842:Bone and Bones / Q000000981:diagnostic imaging / Q000648:ultrastructure; D002454:Cell Differentiation / Q000235:genetics; D018920:Coculture Techniques; D007150:Immunohistochemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D010006:Osteoblasts; D010010:Osteoclasts / Q000502:physiology* / Q000648:ultrastructure; D053495:Osteopontin; D012333:RNA, Messenger / Q000032:analysis; D011859:Radiography; D012795:Sialoglycoproteins / Q000032:analysis / Q000172:deficiency* / Q000235:genetics; D013154:Spleen / Q000166:cytology; D014070:Tooth / Q000254:growth & development* / Q000648:ultrastructure
D012333:RNA, Messenger; D012795:Sialoglycoproteins; C506896:Spp1 protein, mouse; D053495:Osteopontin