Modest Effects of <scp>Osteoclast‐Specific ERα</scp> Deletion after Skeletal Maturity

Estrogen regulates bone mass in women and men, but the underlying cellular mechanisms of estrogen action on remain unclear. Although both receptor (ER)α ERβ are expressed cells, ERα is dominant for skeletal action. Previous studies using either global or cell-specific deletion provided important insights, each these approaches had limitations. Specifically, high circulating sex steroid levels knockout mice effects during growth development constitutive have made it difficult to clearly define role specific cell types adult skeleton. We recently generated characterized with tamoxifen-inducible osteocytes driven by 8-kb Dmp1 promoter (ERαΔOcy mice), revealing detrimental osteocyte-specific trabecular volume (−20.1%) formation rate (−18.9%) female, not male, mice. Here, we developed analogous inducible osteoclasts Cathepsin K (ERαΔOcl mice). In a study design identical that previously described ERαΔOcy mice, ERαΔOcl showed borderline (−10.2%, p = 0.084) reduction volume, no change osteoclast numbers, significant increase serum CTx levels, consistent increased activity. These findings differ from previous osteoclast-specific deletion, which led clear deficits numbers. Collectively, data indicate osteocyte likely more than via conception onward has dramatic osteoclastic © 2023 The Authors. JBMR Plus published Wiley Periodicals LLC behalf American Society Bone Mineral Research.