Regulation of Beta Catenin Signaling and Parathyroid Hormone Anabolic Effects in Bone by the Matricellular Protein Periostin

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2012 Aug 29

PMID 22927401

Citations 73

Authors

Nicolas Bonnet

Simon J Conway

Serge L Ferrari

Affiliations

Soon will be listed here.

Abstract

Periostin (Postn) is a matricellular protein preferentially expressed by osteocytes and periosteal osteoblasts in response to mechanical stimulation and parathyroid hormone (PTH). Whether and how periostin expression influences bone anabolism, however, remains unknown. We investigated the skeletal response of adult Postn(-/-) and Postn(+/+) mice to intermittent PTH. Compared with Postn(+/+), Postn(-/-) mice had a lower bone mass, cortical bone volume, and strength response to PTH. PTH-stimulated bone-forming indices were all significantly lower in Postn(-/-) mice, particularly at the periosteum. Furthermore, in vivo stimulation of Wnt-β-catenin signaling by PTH, as evaluated in TOPGAL reporter mice, was inhibited in the absence of periostin (TOPGAL;Postn(-/-) mice). PTH stimulated periostin and inhibited MEF2C and sclerostin (Sost) expression in bone and osteoblasts in vitro. Recombinant periostin also suppressed Sost expression, which was mediated through the integrin αVβ3 receptor, whereas periostin-blocking antibody prevented inhibition of MEF2C and Sost by PTH. In turn, administration of a Sost-blocking antiboby partially restored the PTH-mediated increase in bone mass in Postn(-/-) mice. In addition, primary osteoblasts from Postn(-/-) mice showed a lower proliferation, mineralization, and migration, both spontaneously and in response to PTH. Osteoblastic gene expression levels confirmed a defect of Postn(-/-) osteoblast differentiation with and without PTH, as well as an increased osteoblast apoptosis in the absence of periostin. These data elucidate the complex role of periostin on bone anabolism, through the regulation of Sost, Wnt-β-catenin signaling, and osteoblast differentiation.

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References

Gillan L, Matei D, Fishman D, Gerbin C, Karlan B, Chang D . Periostin secreted by epithelial ovarian carcinoma is a ligand for alpha(V)beta(3) and alpha(V)beta(5) integrins and promotes cell motility. Cancer Res. 2002; 62(18):5358-64. View

Ogita M, Rached M, Dworakowski E, Bilezikian J, Kousteni S . Differentiation and proliferation of periosteal osteoblast progenitors are differentially regulated by estrogens and intermittent parathyroid hormone administration. Endocrinology. 2008; 149(11):5713-23. PMC: 2584601. DOI: 10.1210/en.2008-0369. View

Clement-Lacroix P, Ai M, Morvan F, Roman-Roman S, Vayssiere B, Belleville C . Lrp5-independent activation of Wnt signaling by lithium chloride increases bone formation and bone mass in mice. Proc Natl Acad Sci U S A. 2005; 102(48):17406-11. PMC: 1297659. DOI: 10.1073/pnas.0505259102. View

He X, Semenov M, Tamai K, Zeng X . LDL receptor-related proteins 5 and 6 in Wnt/beta-catenin signaling: arrows point the way. Development. 2004; 131(8):1663-77. DOI: 10.1242/dev.01117. View

Corren J, Lemanske R, Hanania N, Korenblat P, Parsey M, Arron J . Lebrikizumab treatment in adults with asthma. N Engl J Med. 2011; 365(12):1088-98. DOI: 10.1056/NEJMoa1106469. View

Armstrong V, Muzylak M, Sunters A, Zaman G, Saxon L, Price J . Wnt/beta-catenin signaling is a component of osteoblastic bone cell early responses to load-bearing and requires estrogen receptor alpha. J Biol Chem. 2007; 282(28):20715-27. DOI: 10.1074/jbc.M703224200. View

Reppe S, Stilgren L, Olstad O, Brixen K, Nissen-Meyer L, Gautvik K . Gene expression profiles give insight into the molecular pathology of bone in primary hyperparathyroidism. Bone. 2006; 39(1):189-98. DOI: 10.1016/j.bone.2005.12.020. View

Lindsay R, Cosman F, Zhou H, Bostrom M, Shen V, Cruz J . A novel tetracycline labeling schedule for longitudinal evaluation of the short-term effects of anabolic therapy with a single iliac crest bone biopsy: early actions of teriparatide. J Bone Miner Res. 2006; 21(3):366-73. DOI: 10.1359/JBMR.051109. View

Li X, Liu H, Qin L, Tamasi J, Bergenstock M, Shapses S . Determination of dual effects of parathyroid hormone on skeletal gene expression in vivo by microarray and network analysis. J Biol Chem. 2007; 282(45):33086-97. DOI: 10.1074/jbc.M705194200. View

10.

Ruan K, Bao S, Ouyang G . The multifaceted role of periostin in tumorigenesis. Cell Mol Life Sci. 2009; 66(14):2219-30. PMC: 11115806. DOI: 10.1007/s00018-009-0013-7. View

11.

Jilka R . Molecular and cellular mechanisms of the anabolic effect of intermittent PTH. Bone. 2007; 40(6):1434-46. PMC: 1995599. DOI: 10.1016/j.bone.2007.03.017. View

12.

Kramer I, Loots G, Studer A, Keller H, Kneissel M . Parathyroid hormone (PTH)-induced bone gain is blunted in SOST overexpressing and deficient mice. J Bone Miner Res. 2009; 25(2):178-89. PMC: 3153379. DOI: 10.1359/jbmr.090730. View

13.

Xiao S, Gao Y, Cheung C, Bow C, Lau K, Sham P . Association of CDX1 binding site of periostin gene with bone mineral density and vertebral fracture risk. Osteoporos Int. 2012; 23(7):1877-87. PMC: 3368110. DOI: 10.1007/s00198-011-1861-1. View

14.

Bouxsein M, Pierroz D, Glatt V, Goddard D, Cavat F, Rizzoli R . beta-Arrestin2 regulates the differential response of cortical and trabecular bone to intermittent PTH in female mice. J Bone Miner Res. 2005; 20(4):635-43. PMC: 1586119. DOI: 10.1359/JBMR.041204. View

15.

Robling A, Kedlaya R, Ellis S, Childress P, Bidwell J, Bellido T . Anabolic and catabolic regimens of human parathyroid hormone 1-34 elicit bone- and envelope-specific attenuation of skeletal effects in Sost-deficient mice. Endocrinology. 2011; 152(8):2963-75. PMC: 3138236. DOI: 10.1210/en.2011-0049. View

16.

Lau K, Kapur S, Kesavan C, Baylink D . Up-regulation of the Wnt, estrogen receptor, insulin-like growth factor-I, and bone morphogenetic protein pathways in C57BL/6J osteoblasts as opposed to C3H/HeJ osteoblasts in part contributes to the differential anabolic response to fluid shear. J Biol Chem. 2006; 281(14):9576-88. DOI: 10.1074/jbc.M509205200. View

17.

Martin T, Sims N . Osteoclast-derived activity in the coupling of bone formation to resorption. Trends Mol Med. 2005; 11(2):76-81. DOI: 10.1016/j.molmed.2004.12.004. View

18.

Bianchi E, Ferrari S . Beta-arrestin2 regulates parathyroid hormone effects on a p38 MAPK and NFkappaB gene expression network in osteoblasts. Bone. 2009; 45(4):716-25. PMC: 2741591. DOI: 10.1016/j.bone.2009.06.020. View

19.

Samadfam R, Xia Q, Goltzman D . Co-treatment of PTH with osteoprotegerin or alendronate increases its anabolic effect on the skeleton of oophorectomized mice. J Bone Miner Res. 2006; 22(1):55-63. DOI: 10.1359/jbmr.060915. View

20.

Pierroz D, Rufo A, Bianchi E, Glatt V, Capulli M, Rucci N . Beta-Arrestin2 regulates RANKL and ephrins gene expression in response to bone remodeling in mice. J Bone Miner Res. 2008; 24(5):775-84. PMC: 2672203. DOI: 10.1359/jbmr.081237. View