Age-dependent Wnt gene expression in bone and during the course of osteoblast differentiation

Abstract

Wnt signaling is vital for osteoblast differentiation and recently has been associated with aging. Because impaired osteoblastogenesis is a cellular characteristic of age-induced bone loss, we investigated whether this process is associated with an altered expression of Wnt signaling-related proteins in bone and osteoblasts. Bone marrow cells were isolated from male C57BL/6 mice, aged 6 weeks, 6 months, and 18 months, respectively. Osteogenic differentiation was induced for 3 weeks and assessed using alizarin red staining. Gene expression of Wnt1, 3a, 4, 5a, 5b, 7b, 9b, 10b, lipoprotein receptor-related protein (LRP)-5/6, as well as dickkopf-1 (Dkk-1), sclerostin, and secreted frizzled related protein-1 (sFRP-1) was determined in bone tissue and osteoblasts on days 7, 14, and 21 by realtime RT-PCR. Osteoblast differentiation was significantly reduced in aged mice compared with young and adult mice. In bone tissue, expression levels of all genes assessed were decreased in adult and old mice, respectively, compared with young mice. Mature osteoblasts of aged compared with those of young mice showed enhanced expression of Wnt9b, LRP-6, and Dkk-1, and decreased expression of Wnt5a and 7b. In early osteoblasts, mRNA levels of Wnt1, 5a, 5b, and 7b were increased significantly in aged mice. The expression of Wnt3a, 4, LRP-5, and sclerostin was not altered in aged osteoblasts. In conclusion, osteoblastic expression of each Wnt-related protein is regulated individually by aging. The overall decreased expression of Wnt-related proteins in bone tissue of aged mice underlines the newly discovered association of Wnt signaling with aging.

High serum sclerostin predicts the occurrence of osteoporotic fractures in postmenopausal women: The center of excellence for osteoporosis research study

“…Osteoblastic expression of Wnt-related proteins is modulated by aging. (34) We observed a positive association between sclerostin levels and age. Other studies report increased sclerostin levels with age.…”

Low-dose PTH increases osteoblast activity via decreased Mef2c/Sost in senescent osteopenic mice

“…7). The finding that PTH at low dose is able to modulate specific Wnt signalling effectors in Samp6 mice is particularly important in the context of skeletal senescence because results from current studies indicate that bone ageing is associated with alterations in the local expression of Wnt ligands (Rauner et al 2008) among other mechanisms (Manolagas & Parfitt 2010, Marie 2014. We previously reported that the anti-osteoporotic agent strontium ranelate promotes Wnt signalling in osteoblasts and thereby increases bone formation and bone mass in senescent osteopenic Samp6 mice (Saidak et al 2012).…”

Mutations in WNT1 are a cause of osteogenesis imperfecta

“…Although in situ hybridisation studies have not detected Wnt1 expression during in utero mouse limb development,20 Wnt1 expression can be detected by real-time PCR in postnatal mouse long bones, including osteoblasts 21. Given the predominance of the brain phenotype in the global Wnt1 knockout mouse, this mouse model may not be ideal for elucidating the function of Wnt1 in bone cells.…”