Upregulation of basal TGFbeta1 levels by EMF coincident with chondrogenesis--implications for skeletal repair and tissue engineering.
Members of the TGFbeta/BMP gene family regulate cartilage and bone development. These genes are re-expressed in bone repair and are thought to mediate chondro- and osteoprogenitor cell differentiation. These observations have led to a therapeutic strategy of introducing these growth factors into experimental cartilage and bone defects. Therapeutic efficacy, however, has been limited by diffusion or inactivation of these growth factors from the desired site and by the inability to deliver sustained concentrations of growth factors. This study demonstrates an increase in basal TGFbeta mRNA and protein levels in association with chondrogenic differentiation in endochondral ossification. mRNA is increased by 158%; protein by 23%, and cells immunopositive for TGFbeta by 343% at maximal TGFbeta expression. Importantly, the pattern of TGFbeta expression is preserved throughout the developmental sequence. Our data suggest that the exposure to a specific electromagnetic field (EMF) enhances, but does not disorganize, chondrogenesis and endochondral calcification as well as the normal physiologic expression of TGFbeta. The ability to increase TGFbeta at a moderately low dose for sustained periods of time without disorganizing its physiology suggests the ability to establish temporal concentration gradients of growth factors for the purpose of stimulating skeletal repair.
Aaron
Roy K
RK
Department of Orthopaedics, Brown University School of Medicine, Rhode Island Hospital, Providence, USA. roy_aaron@brown.edu
Wang
Shuo
S
Ciombor
Deborah M
DM
D000818:Animals; D015152:Blotting, Northern; D016723:Bone Remodeling / Q000502:physiology; D002356:Cartilage / Q000378:metabolism / Q000528:radiation effects; D020219:Chondrogenesis / Q000502:physiology / Q000528:radiation effects*; D004574:Electromagnetic Fields; D007150:Immunohistochemistry; D008297:Male; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D013997:Time Factors; D023822:Tissue Engineering / Q000379:methods*; D016212:Transforming Growth Factor beta / Q000096:biosynthesis* / Q000235:genetics; D053773:Transforming Growth Factor beta1; D015854:Up-Regulation / Q000528:radiation effects*
D012333:RNA, Messenger; C508962:Tgfb1 protein, rat; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1