Skip to main content

Advertisement

Log in

Expression of PPARγ and β/δ in Human Primary Osteoblastic Cells: Influence of Polyunsaturated Fatty Acids

  • Published:
Calcified Tissue International Aims and scope Submit manuscript

Abstract

As previously reported, the age-related association between bone loss and increased marrow adipose volume may involve inhibitory effects of polyunsaturated fatty acids (PUFAs) potentially released by medullary adipocytes on osteoblastic proliferation and cell cycle progression. Because PUFAs have been reported to activate peroxisome proliferator-activated receptors (PPARs), we investigated the expression of these nuclear receptors in human primary osteoblastic (hOB) cells and examined the effects of natural PPAR ligands on hOB cell proliferation. We demonstrated basic expressions of PPARγ and PPARβ/δ in hOB cells at the protein level. As already shown for PUFAs, a short-term treatment with 15deoxy-Δ12,14 –prostaglandin J2 (15dPGJ2) or prostacyclin (PGI2), which are specific ligands for PPARγ and PPARβ/δ, respectively, also significantly inhibited hOB cell proliferation. Given that the cell cycle withdrawal resulting from PPARγ activation was often associated with the induction of cell differentiation, long-term effects of PUFAs and 15dPGJ2 were also assessed on the expression levels of transcription factors. PUFAs and 15dPGJ2 enhanced the expression of PPARγ in hOB cells. It is of interest to note that PPARγ protein level was dose-dependently increased, whereas that of Cbfal was decreased by a fatty acid–rich serum. In conclusion, this study shows that PPARγ and β/δ are expressed by hOB cells. The results further suggest that the short-term antiproliferative effect of PUFAs may involve PPAR activation in hOB cells, resulting in a cell cycle withdrawal favorable for the long-term differentiating effects of fatty acids. Further studies are now required to confirm the functional role of PPARs in the antiproliferative effects of PUFAs in hOB cells.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6

Similar content being viewed by others

References

  1. P Meunier J Aaron C Edouard G Vignon (1971) ArticleTitleOsteoporosis and the replacement of cell populations of the marrow by adipose tissue. A quantitative study of 84 iliac bone biopsies Clin Orthop 80 147–154 Occurrence Handle5133320 Occurrence Handle1:STN:280:DyaE38%2FotVansw%3D%3D

    PubMed  CAS  Google Scholar 

  2. AC Maurin PM Chavassieux L Frappart PD Delmas CM Serre PJ Meunier (2000) ArticleTitleInfluence of mature adipocytes on osteoblast proliferation in human primary cocultures Bone 26 485–489 Occurrence Handle10773588 Occurrence Handle1:STN:280:DC%2BD3c3msVensw%3D%3D

    PubMed  CAS  Google Scholar 

  3. AC Maurin PM Chavassieux E Vericel PJ Meunier (2002) ArticleTitleRole of polyunsaturated fatty acids in the inhibitory effect of human adipocytes on osteoblastic proliferation Bone 31 260–266 Occurrence Handle12110443 Occurrence Handle1:CAS:528:DC%2BD38XltFWgs7Y%3D

    PubMed  CAS  Google Scholar 

  4. W Stillwell W Ehringer LJ Jenski (1993) ArticleTitleDocosahexaenoic acid increases permeability of lipid vesicles and tumor cells Lipids 28 103–108 Occurrence Handle8441334 Occurrence Handle1:CAS:528:DyaK3sXhtl2ns74%3D

    PubMed  CAS  Google Scholar 

  5. DB Jump (2002) ArticleTitleDietary polyunsaturated fatty acids and regulation of gene transcription Curr Opin Lipidol 13 155–164 Occurrence Handle11891418 Occurrence Handle1:CAS:528:DC%2BD38XivFKmt74%3D

    PubMed  CAS  Google Scholar 

  6. EJ Corey C Shih JR Cashman (1983) ArticleTitleDocosahexaenoic acid is a strong inhibitor of prostaglandin but not leukotriene biosynthesis Proc Natl Acad Sci USA 80 3581–3584 Occurrence Handle6304720 Occurrence Handle1:CAS:528:DyaL3sXks1GjtL8%3D Occurrence Handle394093

    PubMed  CAS  PubMed Central  Google Scholar 

  7. F Lesage F Maingret M Lazdunski (2000) ArticleTitleCloning and expression of human TRAAK, a polyunsaturated fatty acids-activated and mechano-sensitive K(+) channel FEBS Lett 471 137–140 Occurrence Handle10767409 Occurrence Handle1:CAS:528:DC%2BD3cXitlOltLY%3D

    PubMed  CAS  Google Scholar 

  8. TJ Wilding YH Chai JE Huettner (1998) ArticleTitleInhibition of rat neuronal kainate receptors by cis-unsaturated fatty acids J Physiol 513 331–339 Occurrence Handle9806986 Occurrence Handle2231290 Occurrence Handle1:CAS:528:DyaK1MXhtFeitw%3D%3D

    PubMed  PubMed Central  CAS  Google Scholar 

  9. J Nabekura K Noguchi MR Witt M Nielsen N Akaike (1998) ArticleTitleFunctional modulation of human recombinant gamma-aminobutyric acid type A receptor by docosahexaenoic acid J Biol Chem 273 11056–11061 Occurrence Handle9556589 Occurrence Handle1:CAS:528:DyaK1cXjtFGktbg%3D

    PubMed  CAS  Google Scholar 

  10. R Graber C Sumida EA Nunez (1994) ArticleTitleFatty acids and cell signal transduction J Lipid Mediat Cell Signal 9 91–116 Occurrence Handle8012764 Occurrence Handle1:CAS:528:DyaK2MXhsVegug%3D%3D

    PubMed  CAS  Google Scholar 

  11. B Mirnikjoo SE Brown HF Kim LB Marangell JD Sweatt EJ Weeber (2001) ArticleTitleProtein kinase inhibition by omega-3 fatty acids J Biol Chem 276 10888–10896 Occurrence Handle11152679 Occurrence Handle1:CAS:528:DC%2BD3MXjvFCqurs%3D

    PubMed  CAS  Google Scholar 

  12. S Laurora S Pizzimenti F Briatore A Fraioli M Maggio P Reffo C Ferretti MU Dianzani G Barrera (2003) ArticleTitlePeroxisome proliferator-activated receptor ligands affect growth-related gene expression in human leukemic cells J Pharmacol Exp Ther 305 932–942 Occurrence Handle12649303 Occurrence Handle1:CAS:528:DC%2BD3sXkt1SnsLk%3D

    PubMed  CAS  Google Scholar 

  13. A Sellmayer U Danesch PC Weber (1996) ArticleTitleEffects of different polyunsaturated fatty acids on growth-related early gene expression and cell growth Lipids 31 IssueIDSuppl S37–S40 Occurrence Handle8729091 Occurrence Handle1:CAS:528:DyaK28XhvVShtrs%3D

    PubMed  CAS  Google Scholar 

  14. E Duplus M Glorian C Forest (2000) ArticleTitleFatty acid regulation of gene transcription J Biol Chem 275 30749–30752 Occurrence Handle10934217 Occurrence Handle1:CAS:528:DC%2BD3cXntlCjtLo%3D

    PubMed  CAS  Google Scholar 

  15. JP Pegorier C Le May J Girard (2004) ArticleTitleControl of gene expression by fatty acids J Nutr 134 2444S–2449S Occurrence Handle15333740 Occurrence Handle1:CAS:528:DC%2BD2cXns1ejt7k%3D

    PubMed  CAS  Google Scholar 

  16. AK Hihi L Michalik W Wahli (2002) ArticleTitlePPARs: transcriptional effectors of fatty acids and their derivatives Cell Mol Life Sci 59 790–798 Occurrence Handle12088279 Occurrence Handle1:CAS:528:DC%2BD38XlvFequ78%3D

    PubMed  CAS  Google Scholar 

  17. K Yu W Bayona CB Kallen HP Harding CP Ravera G McMahon M Brown MA Lazar (1995) ArticleTitleDifferential activation of peroxisome proliferator-activated receptors by eicosanoids J Biol Chem 270 23975–23983 Occurrence Handle7592593 Occurrence Handle1:CAS:528:DyaK2MXovVSgsbk%3D

    PubMed  CAS  Google Scholar 

  18. SA Kliewer JM Lenhard TM Willson I Patel DC Morris JM Lehmann (1995) ArticleTitleA prostaglandin J2 metabolite binds peroxisome proliferator-activated receptor gamma and promotes adipocyte differentiation Cell 83 813–819 Occurrence Handle8521498 Occurrence Handle1:CAS:528:DyaK2MXpvVehtb4%3D

    PubMed  CAS  Google Scholar 

  19. BM Forman P Tontonoz J Chen RP Brun BM Spiegelman RM Evans (1995) ArticleTitle15-Deoxy-delta 12, 14-prostaglandin J2 is a ligand for the adipocyte determination factor PPAR gamma Cell 83 803–812 Occurrence Handle8521497 Occurrence Handle1:CAS:528:DyaK2MXpvVehtLc%3D

    PubMed  CAS  Google Scholar 

  20. R Hertz I Berman D Keppler J Bar-Tana (1996) ArticleTitleActivation of gene transcription by prostacyclin analogues is mediated by the peroxisome-proliferators-activated receptor (PPAR) Eur J Biochem 235 242–247 Occurrence Handle8631336 Occurrence Handle1:CAS:528:DyaK28XotlahtQ%3D%3D

    PubMed  CAS  Google Scholar 

  21. DD Diascro RL Vogel SuffixJr TE Johnson KM Witherup SM Pitzenberger SJ Rutledge DJ Prescott GA Rodan A Schmidt (1998) ArticleTitleHigh fatty acid content in rabbit serum is responsible for the differentiation of osteoblasts into adipocyte-like cells J Bone Miner Res 13 96–106 Occurrence Handle9443795 Occurrence Handle1:CAS:528:DyaK1cXltVyqtQ%3D%3D

    PubMed  CAS  Google Scholar 

  22. MG Cecchini J Portenier A Wetterwald O Braissant W Wahli (1997) ArticleTitleExpression of peroxisome proliferator activated receptors in rat bone J Bone Miner Res 12 (suppl 1) IssueIDsuppl 1 S458

    Google Scholar 

  23. ME Nuttall AJ Patton DL Olivera DP Nadeau M Gowen (1998) ArticleTitleHuman trabecular bone cells are able to express both osteoblastic and adipocytic phenotype: implications for osteopenic disorders J Bone Miner Res 13 371–382 Occurrence Handle9525337 Occurrence Handle1:STN:280:DyaK1c7osVanuw%3D%3D

    PubMed  CAS  Google Scholar 

  24. JM Gimble CE Robinson X Wu KA Kelly BR Rodriguez SA Kliewer JM Lehmann DC Morris (1996) ArticleTitlePeroxisome proliferator-activated receptor-gamma activation by thiazolidinediones induces adipogenesis in bone marrow stromal cells Mol Pharmacol 50 1087–1094 Occurrence Handle8913339 Occurrence Handle1:CAS:528:DyaK28XntFCqsrw%3D

    PubMed  CAS  Google Scholar 

  25. B Lecka-Czernik I Gubrij EJ Moerman O Kajkenova DA Lipschitz SC Manolagas RL Jilka (1999) ArticleTitleInhibition of Osf2/Cbfa1 expression and terminal osteoblast differentiation by PPAR gamma 2 J Cell Biochem 74 357–371 Occurrence Handle10412038 Occurrence Handle1:CAS:528:DyaK1MXkvV2hu7g%3D

    PubMed  CAS  Google Scholar 

  26. B Lecka-Czernik EJ Moerman DF Grant JM Lehmann SC Manolagas RL Jilka (2002) ArticleTitleDivergent effects of selective peroxisome proliferator-activated receptor-gamma 2 ligands on adipocyte versus osteoblast differentiation Endocrinology 143 2376–2384 Occurrence Handle12021203 Occurrence Handle1:CAS:528:DC%2BD38XjvFKjurg%3D

    PubMed  CAS  Google Scholar 

  27. MJ Jeon JA Kim SH Kwon SW Kim KS Park SW Park SY Kim CS Shin (2003) ArticleTitleActivation of peroxisome proliferator-activated receptor-γ inhibits the Runx2-mediated transcription of osteocalcin in osteoblasts J Biol Chem 278 23270–23277 Occurrence Handle12704187 Occurrence Handle1:CAS:528:DC%2BD3sXkslygsrY%3D

    PubMed  CAS  Google Scholar 

  28. T Akune S Ohba S Kamekura M Yamaguchi UI Chung N Kubota Y Terauchi Y Harada Y Azuma K Nakamura T Kadowaki H Kawaguchi (2004) ArticleTitlePPAR gamma insufficiency enhances osteogenesis through osteoblast formation from bone marrow progenitors J Clin Invest 113 846–855 Occurrence Handle15067317 Occurrence Handle362117 Occurrence Handle1:CAS:528:DC%2BD2cXisVagtbw%3D

    PubMed  PubMed Central  CAS  Google Scholar 

  29. TA Cock J Back F Elefteriou G Karsenty P Kastner S Chan J Auwerx (2004) ArticleTitleEnhanced bone formation in lipodystrophic PPARγhyp/hyp mice relocates hematopoiesis to the spleen EMBO J 10 1007–1012

    Google Scholar 

  30. MA Sorocéanu D Maio XY Bai H Su D Goltzman AC Karaplis (2004) ArticleTitleRosiglitazone impacts negatively on bone promoting osteoblast/osteocyte apoptosis J Endocrinol 183 203–216 Occurrence Handle15525588

    PubMed  Google Scholar 

  31. SO Rzonca LJ Suva D Gaddy DC Montague B Lecka-Czernik (2004) ArticleTitleBone is a target for the antidiabetic compound rosiglitazone Endocrinol 145 401–406 Occurrence Handle1:CAS:528:DC%2BD3sXhtVWgtL7O

    CAS  Google Scholar 

  32. IE Kelly TS Man K Walsh MEJ Lean (1999) ArticleTitleEffects of a thiazolidinedione compound on body fat and fat distribution of patients with type 2 diabetes Diabetes Care 22 288–293 Occurrence Handle10333947 Occurrence Handle1:STN:280:DyaK1M3ms1Cruw%3D%3D

    PubMed  CAS  Google Scholar 

  33. PA Grimaldi (2001) ArticleTitleThe roles of PPARs in adipocyte differentiation Prog Lipid Res 40 269–281 Occurrence Handle11412892 Occurrence Handle1:CAS:528:DC%2BD3MXltFWhuro%3D

    PubMed  CAS  Google Scholar 

  34. ED Rosen CJ Walkey P Puigserver BM Spiegelman (2000) ArticleTitleTranscriptional regulation of adipogenesis Genes Dev 14 1293–1307 Occurrence Handle10837022 Occurrence Handle1:CAS:528:DC%2BD3cXjvFOgsb8%3D

    PubMed  CAS  Google Scholar 

  35. S Mandrup MD Lane (1997) ArticleTitleRegulating adipogenesis J Biol Chem 272 5367–5370 Occurrence Handle9102400 Occurrence Handle1:CAS:528:DyaK2sXhslamurs%3D

    PubMed  CAS  Google Scholar 

  36. C Bastie D Holst D Gaillard C Jehl-Pietri PA Grimaldi (1999) ArticleTitleExpression of peroxisome proliferator-activated receptor PPARdelta promotes induction of PPARgamma and adipocyte differentiation in 3T3C2 fibroblasts J Biol Chem 274 21920–21925 Occurrence Handle10419513 Occurrence Handle1:CAS:528:DyaK1MXltVymtL4%3D

    PubMed  CAS  Google Scholar 

  37. S Altiok M Xu BM Spiegelman (1997) ArticleTitlePPARgamma induces cell cycle withdrawal: inhibition of E2F/DP DNA-binding activity via down-regulation of PP2A Genes Dev 11 1987–1998 Occurrence Handle9271121 Occurrence Handle316411 Occurrence Handle1:CAS:528:DyaK2sXlsVSmsbc%3D

    PubMed  PubMed Central  CAS  Google Scholar 

  38. D Shao MA Lazar (1997) ArticleTitlePeroxisome proliferator activated receptor gamma, CCAAT/enhancer-binding protein alpha, and cell cycle status regulate the commitment to adipocyte differentiation J Biol Chem 272 21473–21478 Occurrence Handle9261165 Occurrence Handle1:CAS:528:DyaK2sXls1Oju7k%3D

    PubMed  CAS  Google Scholar 

  39. PM Chavassieux C Chenu A Valentin-Opran B Merle PD Delmas DJ Hartmann S Saez PJ Meunier (1990) ArticleTitleInfluence of experimental conditions on osteoblast activity in human primary bone cell cultures J Bone Miner Res 5 337–343 Occurrence Handle2343773 Occurrence Handle1:STN:280:DyaK3c3mtFGgsw%3D%3D

    PubMed  CAS  Google Scholar 

  40. GV Richieri A Anel AM Kleinfeld (1993) ArticleTitleInteractions of long-chain fatty acids and albumin: determination of free fatty acid levels using the fluorescent probe ADIFAB Biochemistry 32 7574–7580 Occurrence Handle8338853 Occurrence Handle1:CAS:528:DyaK3sXks1KjsL8%3D

    PubMed  CAS  Google Scholar 

  41. M Lanotte D Scott TM Dexter TD Allen (1982) ArticleTitleClonal preadipocyte cell lines with different phenotypes derived from murine marrow stroma: factors influencing growth and adipogenesis in vitro J Cell Physiol 111 177–186 Occurrence Handle7045143 Occurrence Handle1:STN:280:DyaL383hsVamuw%3D%3D

    PubMed  CAS  Google Scholar 

  42. ED Rosen BM Spiegelman (2001) ArticleTitlePPARgamma: a nuclear regulator of metabolism, differentiation, and cell growth J Biol Chem 276 37731–37734 Occurrence Handle11459852 Occurrence Handle1:CAS:528:DC%2BD3MXotFOrsbo%3D

    PubMed  CAS  Google Scholar 

  43. A Schmidt N Endo SJ Rutledge R Vogel D Shinar GA Rodan (1992) ArticleTitleIdentification of a new member of the steroid hormone receptor superfamily that is activated by a peroxisome proliferator and fatty acids Mol Endocrinol 6 1634–1641 Occurrence Handle1333051 Occurrence Handle1:CAS:528:DyaK3sXkvV2hs7Y%3D

    PubMed  CAS  Google Scholar 

  44. C Wang M Fu M D’Amico C Albanese JN Zhou M Brownlee MP Lisanti VK Chatterjee MA Lazar RG Pestell (2001) ArticleTitleInhibition of cellular proliferation through IkappaB kinase-independent and peroxisome proliferator-activated receptor gamma-dependent repression of cyclin D1 Mol Cell Biol 21 3057–3010 Occurrence Handle11287611 Occurrence Handle86934 Occurrence Handle1:CAS:528:DC%2BD3MXivFOqsL8%3D

    PubMed  PubMed Central  CAS  Google Scholar 

  45. Y Miwa T Sasaguri H Inoue Y Taba A Ishida T Abumiya (2000) ArticleTitle15-Deoxy-delta(12,14)-prostaglandin J(2) induces G(1) arrest and differentiation marker expression in vascular smooth muscle cells Mol Pharmacol 58 837–844 Occurrence Handle10999955 Occurrence Handle1:CAS:528:DC%2BD3cXntVaksrw%3D

    PubMed  CAS  Google Scholar 

  46. S Wakino U Kintscher S Kim F Yin WA Hsueh RE Law (2000) ArticleTitlePeroxisome proliferator-activated receptor gamma ligands inhibit retinoblastoma phosphorylation and G1→S transition in vascular smooth muscle cells J Biol Chem 275 22435–22441 Occurrence Handle10801895 Occurrence Handle1:CAS:528:DC%2BD3cXlt1egs7o%3D

    PubMed  CAS  Google Scholar 

  47. H Glantschnig F Varga K Klaushofer (1996) ArticleTitleThe cellular protooncogenes c-fos and egr-1 are regulated by prostacyclin in rodent osteoblasts and fibroblasts Endocrinology 137 4536–4541 Occurrence Handle8895314 Occurrence Handle1:CAS:528:DyaK28Xms1Cqt74%3D

    PubMed  CAS  Google Scholar 

  48. J Zhang M Fu X Zhu Y Xiao Y Mou H Zheng MA Akinbami Q Wang YE Chen (2002) ArticleTitlePeroxisome proliferator-activated receptor delta is up-regulated during vascular lesion formation and promotes post-confluent cell proliferation in vascular smooth muscle cells J Biol Chem 277 11505–11512 Occurrence Handle11809753 Occurrence Handle1:CAS:528:DC%2BD38Xis1Kgtro%3D

    PubMed  CAS  Google Scholar 

  49. MF Pittenger AM Mackay SC Beck RK Jaiswal R Douglas JD Mosca MA Moorman DW Simonetti S Craig DR Marshak (1999) ArticleTitleMultilineage potential of adult human mesenchymal stem cells Science 284 143–147 Occurrence Handle10102814 Occurrence Handle1:CAS:528:DyaK1MXitlCnu7o%3D

    PubMed  CAS  Google Scholar 

  50. L Teboul D Gaillard L Staccini H Inadera EZ Amri PA Grimaldi (1995) ArticleTitleThiazolidinediones and fatty acids convert myogenic cells into adipose-like cells J Biol Chem 270 28183–28187 Occurrence Handle7499310 Occurrence Handle1:CAS:528:DyaK2MXps1ahsLY%3D

    PubMed  CAS  Google Scholar 

  51. E Khan Y Abu-Amer (2003) ArticleTitleActivation of peroxisome proliferator-activated receptor-γ inhibits differentiation of preosteoblasts J Lab Clin Med 142 29–34 Occurrence Handle12878983 Occurrence Handle1:CAS:528:DC%2BD3sXls1ertbg%3D

    PubMed  CAS  Google Scholar 

  52. L Pei P Tontonoz (2004) ArticleTitleFat’s loss is bone’s gain J Clin Invest 113 805–806 Occurrence Handle15067310 Occurrence Handle362126 Occurrence Handle1:CAS:528:DC%2BD2cXisVagtLs%3D

    PubMed  PubMed Central  CAS  Google Scholar 

  53. JL Kirkland T Tchkonia T Pirtskhalava J Han I Karagiannides (2002) ArticleTitleAdipogenesis and aging: does aging make fat go MAD? Exp Gerontol 37 757–767 Occurrence Handle12175476 Occurrence Handle1:CAS:528:DC%2BD38XjvVWjtrc%3D

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to P. M. Chavassieux.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Maurin, A.C., Chavassieux, P.M. & Meunier, P.J. Expression of PPARγ and β/δ in Human Primary Osteoblastic Cells: Influence of Polyunsaturated Fatty Acids. Calcif Tissue Int 76, 385–392 (2005). https://doi.org/10.1007/s00223-004-0108-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00223-004-0108-y

Keywords

Navigation