Age-related changes in lamin A/C expression in the osteoarticular system: laminopathies as a potential new aging mechanism.
BACKGROUND
Mutations in lamin A/C have been described as associated to severe changes in bone and joints. In this study we hypothesize that the expression of lamin A/C may play a role in the pathogenesis of age-related diseases in the osteoarticular system.


METHODS
C57BL/6 young and old mice (4 months; n=10 and 24 months; n=10) were sacrificed. Limbs were isolated for histopathological and Western blot analysis. The proportion of cells (osteoblasts and chondrocytes) positive for lamin A/C was quantified by immunohistochemistry. Lamin B1 was used as control. Finally, lamin A/C expression in bone marrow cells was quantified by Western blot.


RESULTS
A significant reduction in lamin A/C was found in osteoblasts of old as compared to young mice (42% versus 76%, p<0.001). Interestingly, lamin A/C but not lamin B1 expression was found in bone matrix with higher levels in young bone. Additionally, a significant reduction in the number of lamin A/C expressing chondrocytes was seen in old mice as compared to young mice (32% versus 84%, p<0.001). Finally, a reduction in lamin A/C expression was found in bone marrow cells obtained from old mice as compared to young mice.


CONCLUSIONS
This is the first assessment of the age-related changes in lamin A/C expression in the osteoarticular system. We conclude that with aging there is a reduction in lamin A/C expression which could have a significance on osteoarticular cells function and viability.
Duque
Gustavo
G
Division of Geriatric Medicine, Jewish General Hospital 3755, McGill University, Chemin de la Cote Sainte Catherine Montreal, Que., Canada H3T 1E2. gustavo.duque@mcgill.ca
Rivas
Daniel
D
D000375:Aging; D000818:Animals; D015153:Blotting, Western; D001854:Bone Marrow Cells / Q000378:metabolism; D002470:Cell Survival; D019902:Chondrocytes / Q000378:metabolism; D004492:Edetic Acid / Q000737:chemistry; D005260:Female; D015870:Gene Expression; D007150:Immunohistochemistry; D034904:Lamin Type A / Q000096:biosynthesis* / Q000378:metabolism; D034921:Lamin Type B / Q000378:metabolism; D034882:Lamins; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D015233:Models, Statistical; D009154:Mutation; D010006:Osteoblasts / Q000378:metabolism; D010024:Osteoporosis
D034904:Lamin Type A; D034921:Lamin Type B; D034882:Lamins; C440308:lamin C; D004492:Edetic Acid