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.

METHODOLOGY

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.

CONCLUSION

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.