The role of canonical Wnt signaling in regulation of strain-related orientation of division was examined using sclerostin, a predominantly osteocyte-derived Wnt antagonist whose expression is downregulated by strain.16 Sclerostin is so potent a regulator of bone formation that sclerostin neutralizing antibodies are currently in clinical trials for the treatment of osteoporosis.70 Pretreatment of osteoblast cultures with sclerostin prevents increased proliferation after strain (Fig. 4A) but does not affect strain's ability to orient cell divisions (Fig. 4B). Here, SOST is linked to osteoporosis.