In an article published in June 2017 issue of the Journal of Bone and Mineral Research, Francesca Fontana, MD, PhD, and colleagues in the laboratory of Roberto Civitelli, MD, report that mice genetically deficient in N-cadherin – a molecule that allows cells to adhere to each other and modulates Wnt signaling – accrue more bone mass than normal mice when given a stimulator of bone formation that activates Wnt signaling. Antibodies against sclerostin, a Wnt inhibitor, are being currently tested in clinical trials for stimulating bone formation and improve bone density in patients with osteoporosis; however, their stimulatory effect wanes after 6-8 months of treatment. Dr. Fontana, in Dr. Civitelli’s group, provides a potential explanation to this waning “osteoanabolic” effect of anti-sclerostin antibodies, and offer a possible target to overcome such therapeutic “escape” phenomenon.
N-cadherin Regulation of Bone Growth and Homeostasis Is Osteolineage Stage-Specific.
Fontana F, Hickman-Brecks CL, Salazar VS, Revollo L, Abou-Ezzi G, Grimston SK, Jeong SY, Watkins M, Fortunato M, Alippe Y, Link DC, Mbalaviele G, Civitelli R.
J Bone Miner Res. 2017 Jun;32(6):1332-1342. doi: 10.1002/jbmr.3112. Epub 2017 Mar 29.
PMID: 28240364