Age-related changes in bone morphology are accelerated in group VIA Phospholipase A2 (iPLA2β)-null mice

Sasanka Ramanadham, Kevin E. Yarasheski, Matthew J. Silva, Mary Wohltmann, Deborah Veis Novack, Blaine A Christiansen, Xiaolin Tu, Sheng Zhang, Xiaoyong Lei, John Turk

Research output: Contribution to journalArticle

41 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)868-881
Number of pages14
JournalAmerican Journal of Pathology
Volume172
Issue number4
DOIs
StatePublished - Apr 2008
Externally publishedYes

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Phospholipases A2
Knockout Mice
Bone and Bones
Osteoblasts
Mesenchymal Stromal Cells
Osteogenesis
Calcium-Independent Phospholipase A2
Adipogenesis
Messenger RNA
Peroxisome Proliferator-Activated Receptors
Osteoclasts
Adipocytes
Arachidonic Acid
Osteoporosis
Cell Differentiation
Phospholipids
Fatty Acids
Stem Cells
Bone Marrow
Fats

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Age-related changes in bone morphology are accelerated in group VIA Phospholipase A2 (iPLA2β)-null mice. / Ramanadham, Sasanka; Yarasheski, Kevin E.; Silva, Matthew J.; Wohltmann, Mary; Novack, Deborah Veis; Christiansen, Blaine A; Tu, Xiaolin; Zhang, Sheng; Lei, Xiaoyong; Turk, John.

In: American Journal of Pathology, Vol. 172, No. 4, 04.2008, p. 868-881.

Research output: Contribution to journalArticle

Ramanadham, S, Yarasheski, KE, Silva, MJ, Wohltmann, M, Novack, DV, Christiansen, BA, Tu, X, Zhang, S, Lei, X & Turk, J 2008, 'Age-related changes in bone morphology are accelerated in group VIA Phospholipase A2 (iPLA2β)-null mice', American Journal of Pathology, vol. 172, no. 4, pp. 868-881. https://doi.org/10.2353/ajpath.2008.070756
Ramanadham, Sasanka ; Yarasheski, Kevin E. ; Silva, Matthew J. ; Wohltmann, Mary ; Novack, Deborah Veis ; Christiansen, Blaine A ; Tu, Xiaolin ; Zhang, Sheng ; Lei, Xiaoyong ; Turk, John. / Age-related changes in bone morphology are accelerated in group VIA Phospholipase A2 (iPLA2β)-null mice. In: American Journal of Pathology. 2008 ; Vol. 172, No. 4. pp. 868-881.
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