TY - JOUR
T1 - Age-related changes in bone morphology are accelerated in group VIA Phospholipase A2 (iPLA2β)-null mice
AU - Ramanadham, Sasanka
AU - Yarasheski, Kevin E.
AU - Silva, Matthew J.
AU - Wohltmann, Mary
AU - Novack, Deborah Veis
AU - Christiansen, Blaine
AU - Tu, Xiaolin
AU - Zhang, Sheng
AU - Lei, Xiaoyong
AU - Turk, John
PY - 2008/4
Y1 - 2008/4
N2 - Phospholipases A2 (PLA2) hydrolyze the sn-2 fatty acid substituent, such as arachidonic acid, from phospholipids, and arachidonate metabolites are recognized mediators of bone modeling. We have previously generated knockout (KO) mice lacking the group VIA PLA2 (iPLA 2β), which participates in a variety of signaling events; iPLA2β mRNA is expressed in bones of wild-type (WT) but not KO mice. Cortical bone size, trabecular bone volume, bone mineralizing surfaces, and bone strength are similar in WT and KO mice at 3 months and decline with age in both groups, but the decreases are more pronounced in KO mice. The lower bone mass phenotype observed in KO mice is not associated with an increase in osteoclast abundance/activity or a decrease in osteoblast density, but is accompanied by an increase in bone marrow fat. Relative to WT mice, undifferentiated bone marrow stromal cells (BMSCs) from KO mice express higher levels of PPAR-γ and lower levels of Runx2 mRNA, and this correlates with increased adipogenesis and decreased osteogenesis in BMSCs from these mice. In summary, our studies indicate that age-related losses in bone mass and strength are accelerated in iPLA2β-null mice. Because adipocytes and osteoblasts share acommonmesenchymal stem cell origin, our findings suggest that absence of iPLA2β causes abnormalities in osteoblast function and BMSC differentiation and identify a previously unrecognized role of iPLA2β in bone formation.
AB - Phospholipases A2 (PLA2) hydrolyze the sn-2 fatty acid substituent, such as arachidonic acid, from phospholipids, and arachidonate metabolites are recognized mediators of bone modeling. We have previously generated knockout (KO) mice lacking the group VIA PLA2 (iPLA 2β), which participates in a variety of signaling events; iPLA2β mRNA is expressed in bones of wild-type (WT) but not KO mice. Cortical bone size, trabecular bone volume, bone mineralizing surfaces, and bone strength are similar in WT and KO mice at 3 months and decline with age in both groups, but the decreases are more pronounced in KO mice. The lower bone mass phenotype observed in KO mice is not associated with an increase in osteoclast abundance/activity or a decrease in osteoblast density, but is accompanied by an increase in bone marrow fat. Relative to WT mice, undifferentiated bone marrow stromal cells (BMSCs) from KO mice express higher levels of PPAR-γ and lower levels of Runx2 mRNA, and this correlates with increased adipogenesis and decreased osteogenesis in BMSCs from these mice. In summary, our studies indicate that age-related losses in bone mass and strength are accelerated in iPLA2β-null mice. Because adipocytes and osteoblasts share acommonmesenchymal stem cell origin, our findings suggest that absence of iPLA2β causes abnormalities in osteoblast function and BMSC differentiation and identify a previously unrecognized role of iPLA2β in bone formation.
UR - http://www.scopus.com/inward/record.url?scp=42049109481&partnerID=8YFLogxK
U2 - 10.2353/ajpath.2008.070756
DO - 10.2353/ajpath.2008.070756
M3 - Article
C2 - 18349124
AN - SCOPUS:42049109481
SN - 0002-9440
VL - 172
SP - 868
EP - 881
JO - American Journal of Pathology
JF - American Journal of Pathology
IS - 4
ER -