title: Mechanical strain promotes osteoblast ECM formation and improves its osteoinductive potential.
abstract: BACKGROUND
  The extracellular matrix (ECM) provides a supportive microenvironment for cells, which is suitable as a tissue engineering scaffold. Mechanical stimulus plays a significant role in the fate of osteoblast, suggesting that it regulates ECM formation. Therefore, we investigated the influence of mechanical stimulus on ECM formation and bioactivity.
  
  
  METHODS
  Mouse osteoblastic MC3T3-E1 cells were cultured in cell culture dishes and stimulated with mechanical tensile strain. After removing the cells, the ECMs coated on dishes were prepared. The ECM protein and calcium were assayed and MC3T3-E1 cells were re-seeded on the ECM-coated dishes to assess osteoinductive potential of the ECM.
  
  
  RESULTS
  The cyclic tensile strain increased collagen, bone morphogenetic protein 2 (BMP-2), BMP-4, and calcium levels in the ECM. Compared with the ECM produced by unstrained osteoblasts, those of mechanically stimulated osteoblasts promoted alkaline phosphatase activity, elevated BMP-2 and osteopontin levels and mRNA levels of runt-related transcriptional factor 2 (Runx2) and osteocalcin (OCN), and increased secreted calcium of the re-seeded MC3T3-E1 cells.
  
  
  CONCLUSIONS
  Mechanical strain promoted ECM production of osteoblasts in vitro, increased BMP-2/4 levels, and improved osteoinductive potential of the ECM. This study provided a novel method to enhance bioactivity of bone ECM in vitro via mechanical strain to osteoblasts.
authors.affiliation: Academy of Military Medical Science, Tianjin Institute of Medical Equipment, No 106 Wandong Road, Hedong District, Tianjin, 300161, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Guo
authors.forename: Chun-qiu
authors.initials: CQ
authors.lastname: Zhang
authors.forename: Qiang-cheng
authors.initials: QC
authors.lastname: Zeng
authors.forename: Rui-xin
authors.initials: RX
authors.lastname: Li
authors.forename: Lu
authors.initials: L
authors.lastname: Liu
authors.forename: Qin-xin
authors.initials: QX
authors.lastname: Hao
authors.forename: Cai-hong
authors.initials: CH
authors.lastname: Shi
authors.forename: Xi-zheng
authors.initials: XZ
authors.lastname: Zhang
authors.forename: Yu-xian
authors.initials: YX
authors.lastname: Yan
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000378:metabolism; D055415:Bone Morphogenetic Protein 4 / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics; D005109:Extracellular Matrix / Q000378:metabolism*; D006909:Hydroxyproline / Q000378:metabolism; D051379:Mice; D010006:Osteoblasts / Q000166:cytology*; D015675:Osteocalcin / Q000235:genetics; D053495:Osteopontin / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013314:Stress, Mechanical; D013718:Tensile Strength
chemical_list: C525719:Bmp2 protein, mouse; C525810:Bmp4 protein, mouse; D055396:Bone Morphogenetic Protein 2; D055415:Bone Morphogenetic Protein 4; D050659:Core Binding Factor Alpha 1 Subunit; D012333:RNA, Messenger; D015675:Osteocalcin; D053495:Osteopontin; D000469:Alkaline Phosphatase; D006909:Hydroxyproline; D002118:Calcium