Sclerostin, an osteocyte-derived protein coded by the SOST gene, is a direct inhibitor of the Wnt/β-catenin signaling pathway which plays a key role in the bone response to mechanical loading. Previous data demonstrate opposite changes in SOST mRNA expression in metaphyseal vs. diaphyseal bone compartments exposed to 3 days of disuse. No studies have confirmed whether alterations in sclerostin with disuse vary by bone compartments.
PURPOSE: The goal of the current study was to evaluate prevalence of sclerostin-positive osteocytes (%Scl+) in the cortical bone of the mid-shaft femur (cort-MSF) and distal femur metaphysis (cort-DFM) and DFM cancellous bone (can-DFM) after disuse with and without concurrent progressive resistive exercise. We hypothesized %Scl+ would not respond uniformly to disuse and loading in these 3 different bone compartments.
METHODS: Male Sprague Dawley rats (6-7 mo. old) were randomly assigned to cage activity control (CC), hindlimb unloading (HU) for 28 days, and HU with progressive resistive exercise 3 days/week (HU+RE). Excised right femora were scanned at the midshaft and distal femur with peripheral quantitative computed tomography (pQCT). Longitudinal sections of the left distal femora were immunostained and analyzed for %Scl+ in the cort-MSF, cort-DFM, and can-DFM compartments.
RESULTS: Bone mass pQCT measures declined in HU compared to CC (p<0.05), but were preserved in HU+RE. There were no differences in %Scl+ in the 3 bone compartments across the different groups. Within CC bone compartments, cort-DFM trended towards lower %Scl+ compared to cort-MSF (p=0.06). Within HU+RE, cort-DFM %Scl+ was significantly lower than can-DFM (p<0.01) and trended to be lower than cort-MSF (p=0.07).
CONCLUSIONS: HU caused a decline in DFM bone mass while resistive exercise during HU preserved mass; however, %Scl+ was not detectably altered within a single bone compartment across groups. Differences among the 3 compartments within groups were evident at cort-DFM with a decline in %Scl+ in both groups that experienced some loading (CC and HU+RE). Future studies should address longer periods of disuse and loading to elucidate the complexities of SOST and sclerostin expression across bone compartments.
Funded by ACSM NASA Space Research Grant