SCLEROSTIN IMMUNOREACTIVITY INCREASES WITHIN THE CORTICAL BONE OSTEOCYTES IN THE FEMUR OF AGING MICE

Abstract

Sclerostin, a secreted glycoprotein, is known to down-regulate osteocyte differentiation from osteoblasts and acts as a negative modulator of bone formation. It is well established that serum sclerostin levels increase with age but the relationship between changes of cellular expression of sclerostin with age is not well known. Immunohistochemical staining and confocal microscopic analysis of sclerostin immunoreactivity (sclerostin-IR) in the femurs of 4, 9, and 24 month old adult C3H/HeJ male mice was performed. Detectable levels of sclerostin-IR were found in cortical bone osteocytes of the femur in all age groups using an antibody directed against sclerostin. Phalloidin and DAPI were used to mark all osteocytes in cortical bone to detect osteocyte/ sclerostin-IR colocalization. Sclerostin-negative and sclerostin-positive expressing osteocytes were detected in close proximity throughout the cortical bone. Only a subset of osteocytes expressed sclerostin and this ratio of sclerostin positive osteocytes increased with age, from 38.5 ± 1.6% to 43 ± 3.6% to 49 ± 2.3% in young, middle-aged, and old mice, respectively. Understanding the potential mechanisms that drive these age-related changes may influence the therapeutic potential of age-related diseases like osteoporosis.