Deficiency of the intermediate filament synemin reduces bone mass in vivo.
While the type IV intermediate filament protein, synemin, has been shown to play a role in striated muscle and neuronal tissue, its presence and function have not been described in skeletal tissue. Here, we report that genetic ablation of synemin in 14-wk-old male mice results in osteopenia that includes a more than 2-fold reduction in the trabecular bone fraction in the distal femur and a reduction in the cross-sectional area at the femoral middiaphysis due to an attendant reduction in both the periosteal and endosteal perimeter. Analysis of serum markers of bone formation and static histomorphometry revealed a statistically significant defect in osteoblast activity and osteoblast number in vivo. Interestingly, primary osteoblasts isolated from synemin-null mice demonstrate markedly enhanced osteogenic capacity with a concomitant reduction in cyclin D1 mRNA expression, which may explain the loss of osteoblast number observed in vivo. In total, these data suggest an important, previously unknown role for synemin in bone physiology.
Department of Orthopaedics, University of Maryland School of Medicine, Baltimore, Maryland; and.
Megan C
MC
Moorer
Department of Orthopaedics, University of Maryland School of Medicine, Baltimore, Maryland; and.
Atum M
AM
Buo
Department of Physiology, University of Maryland School of Medicine, Baltimore, Maryland.
Karla P
KP
Garcia-Pelagio
Department of Orthopaedics, University of Maryland School of Medicine, Baltimore, Maryland; and jstains@som.umaryland.edu.
Joseph P
JP
Stains
Department of Physiology, University of Maryland School of Medicine, Baltimore, Maryland.
Robert J
RJ
Bloch
D000818:Animals; D015415:Biomarkers / Q000097:blood; D015519:Bone Density / Q000502:physiology*; D001851:Bone Diseases, Metabolic / Q000378:metabolism / Q000503:physiopathology; D000071556:Cancellous Bone / Q000378:metabolism* / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology; D019938:Cyclin D1 / Q000378:metabolism; D005269:Femur / Q000378:metabolism* / Q000502:physiology; D007381:Intermediate Filament Proteins / Q000378:metabolism*; D007382:Intermediate Filaments / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018482:Muscle, Skeletal / Q000378:metabolism / Q000502:physiology; D010006:Osteoblasts / Q000378:metabolism / Q000502:physiology; D010012:Osteogenesis / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism
D015415:Biomarkers; D007381:Intermediate Filament Proteins; D012333:RNA, Messenger; C430456:desmuslin; D019938:Cyclin D1
AKAP; cortical bone; intermediate filament; osteoblasts; synemin; trabecular bone