title: Hormone-sensitive lipase-knockout mice maintain high bone density during aging.
abstract: We tested the hypothesis that the actions of hormone-sensitive lipase (HSL) affect the microenvironment of the bone marrow and that removal of HSL function by gene deletion maintains high bone mass in aging mice. We compared littermate control wild-type (WT) and HSL(-/-) mice during aging for changes in serum biochemical values, trabecular bone density using micro-computed tomography, bone histomorphometry, and characteristics of primary bone marrow cells and preosteoblasts. There is a regulated expression of HSL and genes involved in lipid metabolism in the bone marrow during aging. HSL(-/-) mice have increased serum levels of insulin and osteocalcin with decreased leptin levels. Compared with the marked adipocyte infiltration in WT bone marrow (65% by area) at 14 mo, HSL(-/-) mice have fewer (16%, P<0.05) and smaller adipocytes in bone marrow. While peak bone density is similar, HSL(-/-) mice maintain a higher bone density (bone volume/total volume 6.1%) with age than WT mice (2.6%, P<0.05). Primary osteoblasts from HSL(-/-) mice show increased growth rates and higher osteogenic potential, manifested by increased expression of Runx2 (3.5-fold, P<0.05) and osteocalcin (4-fold, P<0.05). The absence of HSL directs cells within the bone marrow toward osteoblast differentiation and favors the maintenance of bone density with aging.
authors.affiliation: Division of Endocrinology, Stanford University, Stanford, CA 94305-5103, USA.
authors.forename: Wen-Jun
authors.initials: WJ
authors.lastname: Shen
authors.forename: Li-Fen
authors.initials: LF
authors.lastname: Liu
authors.forename: Shailja
authors.initials: S
authors.lastname: Patel
authors.forename: Fredric B
authors.initials: FB
authors.lastname: Kraemer
mesh_terms: D017667:Adipocytes / Q000166:cytology / Q000378:metabolism; D000375:Aging / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D015519:Bone Density / Q000235:genetics / Q000502:physiology*; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism; D016723:Bone Remodeling / Q000235:genetics / Q000502:physiology; D002452:Cell Count; D002454:Cell Differentiation; D048429:Cell Size; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics / Q000378:metabolism; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D007328:Insulin / Q000097:blood; D020738:Leptin / Q000097:blood; D050356:Lipid Metabolism / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism; D015675:Osteocalcin / Q000097:blood / Q000235:genetics / Q000378:metabolism; D002787:Sterol Esterase / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D017154:Stromal Cells / Q000166:cytology / Q000378:metabolism
chemical_list: D050659:Core Binding Factor Alpha 1 Subunit; D007328:Insulin; D020738:Leptin; C493716:Runx2 protein, mouse; D015675:Osteocalcin; D002787:Sterol Esterase