TitleSclerostin antibody treatment rescues the osteopenic bone phenotype of TGFβ inducible early gene-1 knockout female mice.
Publication TypeJournal Article
Year of Publication2020
AuthorsGingery, A, Subramaniam, M, Pitel, KS, Li, X, Ke, HZ, Turner, RT, Iwaniec, UT, Hawse, JR
JournalJ Cell Physiol
Date Published07/2020

Deletion of TGFβ inducible early gene-1 (TIEG) in mice results in an osteopenic phenotype that exists only in female animals. Molecular analyses on female TIEG knockout (KO) mouse bones identified increased expression of sclerostin, an effect that was confirmed at the protein level in serum. Sclerostin antibody (Scl-Ab) therapy has been shown to elicit bone beneficial effects in multiple animal model systems and human clinical trials. For these reasons, we hypothesized that Scl-Ab therapy would reverse the low bone mass phenotype of female TIEG KO mice. In this study, wildtype (WT) and TIEG KO female mice were randomized to either vehicle control (Veh, n = 12/group) or Scl-Ab therapy (10 mg/kg, 1×/wk, s.c.; n = 12/group) and treated for 6 weeks. Following treatment, bone imaging analyses revealed that Scl-Ab therapy significantly increased cancellous and cortical bone in the femur of both WT and TIEG KO mice. Similar effects also occurred in the vertebra of both WT and TIEG KO animals. Additionally, histomorphometric analyses revealed that Scl-Ab therapy resulted in increased osteoblast perimeter/bone perimeter in both WT and TIEG KO animals, with a concomitant increase in P1NP, a serum marker of bone formation. In contrast, osteoclast perimeter/bone perimeter and CTX-1 serum levels were unaffected by Scl-Ab therapy, irrespective of mouse genotype. Overall, our findings demonstrate that Scl-Ab therapy elicits potent bone-forming effects in both WT and TIEG KO mice and effectively increases bone mass in female TIEG KO mice.

Alternate JournalJ. Cell. Physiol.
PubMed ID31975377
PubMed Central IDPMC7359718
Grant ListF32 AR053983 / AR / NIAMS NIH HHS / United States
/ / Mayo Foundation for Medical Education and Research /
DE14036 (JRH and MS) / NH / NIH HHS / United States
T32AR056950 (AG) / NH / NIH HHS / United States
R01 DE014036 / DE / NIDCR NIH HHS / United States
F32AR49823 (AG) / NH / NIH HHS / United States
/ / The Eisenberg Foundation /