Partial prevention of glucocorticoid-induced osteocyte deterioration in young male mice with osteocrin gene therapy
Courtney M. Mazur,
Christian D. Castro Andrade,
Nicha Tokavanich,
Tadatoshi Sato,
Michael Bruce,
Daniel J. Brooks,
Mary L. Bouxsein,
Jialiang S. Wang,
Marc N. Wein
Affiliations
Courtney M. Mazur
Endocrine Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
Christian D. Castro Andrade
Endocrine Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
Nicha Tokavanich
Endocrine Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
Tadatoshi Sato
Endocrine Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
Michael Bruce
Endocrine Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
Daniel J. Brooks
Endocrine Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Center for Advanced Orthopedic Studies, Department of Orthopedic Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
Mary L. Bouxsein
Endocrine Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Center for Advanced Orthopedic Studies, Department of Orthopedic Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
Jialiang S. Wang
Endocrine Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
Marc N. Wein
Endocrine Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Broad Institute of Harvard and MIT, Cambridge, MA, USA; Harvard Stem Cell Institute, Cambridge, MA, USA; Corresponding author
Summary: Glucocorticoid excess suppresses osteocyte remodeling of surrounding bone minerals, causes apoptosis of osteoblasts and osteocytes, and disrupts bone remodeling, eventually, leading to glucocorticoid-induced osteoporosis and bone fragility. Preventing apoptosis and preserving osteocyte morphology could be an effective means of preventing bone loss during glucocorticoid treatment. We hypothesized that osteocrin, which preserves osteocyte viability and morphology in Sp7-deficient mice, could prevent osteocyte death and dysfunction in a glucocorticoid excess model. We used adeno-associated virus (AAV8) to induce osteocrin overexpression in mice one week before implantation with prednisolone or placebo pellets. After 28 days, prednisolone caused the expected reduction in cortical bone thickness and osteocyte canalicular length in control AAV8-treated mice, and these effects were blunted in mice receiving AAV8-osteocrin. Glucocorticoid-induced changes in cortical porosity, trabecular bone mass, and gene expression were not prevented by osteocrin. These findings support a modest therapeutic potential for AAV8-osteocrin in preserving osteocyte morphology during disease.
