Raloxifene Stimulates Estrogen Signaling to Protect Against Age- and Sex-Related Intervertebral Disc Degeneration in Mice

• DOI: 10.3389/fbioe.2022.924918
• Publication Date: 2022-08-11T11:45:24Z
• Authors: Neharika Bhadouria; Alycia G. Berman; Joseph M. Wallace; Nilsson Holguin
• Keywords: Raloxifene; Intervertebral Disc; Degeneration (medical)

Estrogen agonist raloxifene is an FDA-approved treatment of osteoporosis in postmenopausal women, which may also be a promising prophylactic for painful intervertebral disc (IVD) degeneration. Here, we hypothesized that 1) aging and biological sex contribute to IVD degeneration by reducing estrogen signaling 2) stimulates protect against age- sex-related mice. 2.5-month-old (male female) 22.5-month-old (female) C57Bl/6J mice were subcutaneously injected with hydrochloride 5x/week 6 weeks (n = 7-9/grp). Next, female ovariectomized (OVX) or sham operated at 4 months age tissues harvested 5-6/grp). Advanced OVX increased score, weakened strength, reduced receptor-α (ER-α) protein expression, neurotransmitter substance P (SP) expression. Similar compared male IVDs, IVDs more degenerated, mechanically less viscoelastic, expressed ER-α protein, but unlike the effect induced OVX, mechanical force was greater females than males. Therapeutically, systemic injection promoted quell these dysregulations enlarging height, alleviating increasing strength viscoelastic properties IVD, cell expression SP young-adult old Transcriptionally, upregulated gene extracellular matrix-related anabolism IVD. In vertebra, advanced trabecular BV/TV, whereas BV/TV mice, not aging, (females > males) number SP-expressing osteocytes, osteocytes Overall, normalized dysregulation structure, mechanics, pain-related cells sex. These data suggest that, addition bone loss, relieve women age, sex, depletion.