title: Mechanical loading stimulates BMP7, but not BMP2, production by osteocytes.
abstract: Bone mechanical adaptation is a cellular process that allows bones to adapt their mass and structure to mechanical loading. This process is governed by the osteocytes, which in response to mechanical loading produce signaling molecules that affect osteoblasts and osteoclasts. Bone morphogenic proteins (BMPs) are excellent candidates as signaling molecules, but it is unknown whether mechanically stimulated osteocytes affect bone adaptation through BMP production. Therefore, the aim of this study was to assess whether osteocytes produce BMPs in response to mechanical loading. In addition, since BMP7 has a vitamin D receptor (VDR) response element in the promoter region, we also investigated whether VDR is involved in the BMP7 response to mechanical loading. Human or VDR(-/-) mouse primary bone cells were submitted in vitro to 1 h pulsating fluid flow (PFF) and postincubated without PFF (PI) for 1-24 h, and gene and protein expression of BMP2 and BMP7 were quantified. In human bone cells, PFF did not change BMP2 gene expression, but it upregulated BMP7 gene expression by 4.4- to 5.6-fold at 1-3 h PI and stimulated BMP7 protein expression by 2.4-fold at 6 h PI. PFF did not stimulate BMP7 gene expression in VDR(-/-) mouse bone cells. These results show for the first time that mechanical loading upregulates BMP7, likely via the VDR, but not BMP2, gene and protein expression in osteocytes in vitro. Since BMP7 plays a major role in bone development and remodeling, these data might contribute to a better understanding of the mechanism leading to the mechanical adaptation of bone.
authors.affiliation: Department of Oral Cell Biology, Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam and VU University Amsterdam, Research Institute MOVE, Gustav Mahlerlaan, LA, The Netherlands.
authors.forename: Ana
authors.initials: A
authors.lastname: Santos
authors.forename: Astrid D
authors.initials: AD
authors.lastname: Bakker
authors.forename: Hubertine M E
authors.initials: HM
authors.lastname: Willems
authors.forename: Nathalie
authors.initials: N
authors.lastname: Bravenboer
authors.forename: Antonius L J J
authors.initials: AL
authors.lastname: Bronckers
authors.forename: Jenneke
authors.initials: J
authors.lastname: Klein-Nulend
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000235:genetics* / Q000378:metabolism; D055419:Bone Morphogenetic Protein 7 / Q000235:genetics* / Q000378:metabolism; D016466:CHO Cells; D002478:Cells, Cultured; D006224:Cricetinae; D003412:Cricetulus; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008875:Middle Aged; D010011:Osteocytes / Q000378:metabolism* / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D018167:Receptors, Calcitriol / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D013314:Stress, Mechanical; D016474:Weight-Bearing / Q000502:physiology*; D055815:Young Adult
chemical_list: C525718:BMP2 protein, human; C525819:BMP7 protein, human; D055396:Bone Morphogenetic Protein 2; D055419:Bone Morphogenetic Protein 7; D018167:Receptors, Calcitriol