The Matricellular Protein Periostin Is Required for Sost Inhibition and the Anabolic Response to Mechanical Loading and Physical Activity

Bonnet, Nicolas; Standley, Kara N.; Bianchi, Estelle N.; Stadelmann, Vincent A.; Foti, Michelangelo; Conway, Simon J.; Ferrari, Serge

doi:10.1074/jbc.m109.060335

Cited by 184 publications

(215 citation statements)

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“…Interestingly, an interaction between Postn and Sost gene polymorphisms has recently been found in an association study of subjects with extreme-BMD (25). We had previously reported that Postn is necessary for the bone anabolic response to mechanical stimuli (19). At that time we did speculate that the mechanotransduction properties of bone could be impaired because of an alteration of the bone matrix quality, or alternatively, that Postn could directly regulate Sost.…”

Section: Discussionmentioning

confidence: 86%

“…However, in UMR-106 cells, about half of Sost inhibition by PTH appeared independent of Postn. Furthermore, Sost-blocking antibodies did not restore PTH effects in vivo in Postn −/− mice, whereas they did restore the bone anabolic effects of mechanical stimuli (19). Indeed, these observations lead us to propose that PTH down-regulation of Sost in osteocytes is mediated by a two-step process [i.e., through PTH1R activation and cAMP/ERK signaling (probably a rapid and short term effect)], that is independent of Postn (20), then through Postn production and an autocrine/paracrine activation of integrin signaling, leading to a prolonged suppression of Sost expression.…”

Section: Discussionmentioning

confidence: 99%

“…Postn-deficient mice develop periodontitis and osteoporosis (18). We recently reported that Postn mRNA and protein levels are rapidly up-regulated by mechanical stimuli and could contribute to Sost inhibition (19). Indeed, the cortical bone response to mechanical loading was absent in Postn −/− mice but was rescued by Sost-blocking antibodies.…”

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confidence: 99%

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Regulation of beta catenin signaling and parathyroid hormone anabolic effects in bone by the matricellular protein periostin

Bonnet

Conway

Ferrari

2012

Proc. Natl. Acad. Sci. U.S.A.

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128

106

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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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Section: Discussionmentioning

confidence: 86%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Regulation of beta catenin signaling and parathyroid hormone anabolic effects in bone by the matricellular protein periostin

Bonnet

Conway

Ferrari

2012

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

128

106

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“…5-lm sagittal sections of distal femurs were cut with a Polycut E microtome (Leica Corp. Microsystems AG, Glattbrugg, Switzerland) and mounted unstained for fluorescence visualization or stained with modified Goldner's trichrome. Histomorphometric measurements were carried out on the endocortical and periosteal surfaces of femoral midshaft sections and on the secondary spongiosa of distal femur sections using a Leica Q image analyzer at 409 magnification as previously described [18].…”

Section: Histological and Histomorphometric Analysismentioning

confidence: 99%

“…Total RNA was extracted from murine femurs or primary osteoblasts using peqGOLD TriFast TM (peqlab Biotechnologie GmbH) and purified using an RNeasy Mini Kit (Qiagen) [18]. Single-stranded cDNA was synthesized from 2 lg of total RNA using a High-Capacity cDNA Archive Kit (Applied Biosystems) according to the manufacturer's instructions.…”

Section: Rna Isolation Rt-pcr and Real-time Pcrmentioning

confidence: 99%

The p38α MAPK positively regulates osteoblast function and postnatal bone acquisition

Thouverey

Caverzasio

2012

Cell. Mol. Life Sci.

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Bone continuously remodels throughout life by coordinated actions of osteoclasts and osteoblasts. Abnormalities in either osteoclast or osteoblast functions lead to bone disorders. The p38 MAPK pathway has been shown to be essential in controlling osteoblast differentiation and skeletogenesis. Although p38a is the most abundant p38 member in osteoblasts, its specific individual contribution in regulating postnatal osteoblast activity and bone metabolism is unknown. To elucidate the specific role of p38a in regulating osteoblast function and bone homeostasis, we generated mice lacking p38a in differentiated osteoblasts. Osteoblast-specific p38a knockout mice were of normal weight and size. Despite non-significant bone alterations until 5 weeks of age, mutant mice demonstrated significant and progressive decrease in bone mineral density from that age. Adult mice deficient in p38a in osteoblasts displayed a striking reduction in cancellous bone volume at both axial and appendicular skeletal sites. At 6 months of age, trabecular bone volume was reduced by 62 % in those mice. Mutant mice also exhibited progressive decrease in cortical thickness of long bones. These abnormalities correlated with decreased endocortical and trabecular bone formation rate and reduced expressions of type 1 collagen, alkaline phosphatase, osteopontin and osteocalcin whereas bone resorption and osteoclasts remained unaffected. Finally, osteoblasts lacking p38a showed impaired marker gene expressions and defective mineralization in vitro. These findings indicate that p38a is an essential positive regulator of osteoblast function and postnatal bone formation in vivo.

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The Composition of Bone

Boskey

Robey

2013

Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism

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The Matricellular Protein Periostin Is Required for Sost Inhibition and the Anabolic Response to Mechanical Loading and Physical Activity

Abstract: Periostin (gene

Cited by 184 publications

References 59 publications

Regulation of beta catenin signaling and parathyroid hormone anabolic effects in bone by the matricellular protein periostin

Regulation of beta catenin signaling and parathyroid hormone anabolic effects in bone by the matricellular protein periostin

The p38α MAPK positively regulates osteoblast function and postnatal bone acquisition

The Composition of Bone

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