Hoge, M. | Search bioRxiv

bioRxiv2026

The Role of Osteocyte Estrogen Receptor β in Bone Mass Maintenance and Tibial Stiffness Following Sex Hormone Withdrawal in Male and Female Mice

Sex hormones are essential regulators of skeletal maintenance, but the cell-specific mechanisms by which osteocytes mediate the skeletal consequences of sex hormone deficiency remain incompletely understood. Osteocyte estrogen receptor {beta} (Ot-ER{beta}) has been implicated in sex-specific regulation of bone mass, particularly in male mice, yet its role in coordinating bone morphology and mechanical competence following sex hormone withdrawal is unclear. In this study, male and female mice with osteocyte-targeted ER{beta} deletion (ER{beta}-dOT) and littermate controls were subjected to orchiectomy (ORX), ovariectomy (OVX), or sham surgery at 20 weeks of age. Four weeks later, vertebral and tibial bone morphology were assessed by micro-computed tomography, and tibial mechanical behavior was evaluated using strain gauge-calibrated, microCT-based finite element modeling. ORX induced substantial cancellous bone loss in the lumbar vertebra and proximal tibia of male mice regardless of genotype. In cortical bone, however, ORX reduced tibial cortical area and minimum moment of inertia in male littermate controls, whereas these cortical deficits were attenuated in male ER{beta}-dOT mice. Consistent with these morphological changes, ORX increased finite element-predicted peak tensile and compressive strains in tibial cortical and cancellous compartments and reduced whole-bone stiffness in male controls, but these mechanical deteriorations were largely prevented by Ot-ER{beta} deletion. In contrast, OVX produced modest changes in female tibial cortical geometry and increased cancellous bone strains, but these responses were not strongly dependent on Ot-ER{beta}. Together, these findings reveal that Ot-ER{beta} mediates the skeletal response to sex hormone withdrawal in a sex- and compartment-dependent manner. Specifically, Ot-ER{beta} contributes to ORX-induced deterioration of tibial cortical morphology and mechanical competence in male mice, whereas it is largely dispensable for OVX-induced skeletal changes in female mice. This work highlights osteocyte ER{beta} as a sex-specific regulator linking hormonal status, bone morphology, and load-induced strain environments.

bioengineering↗

bioRxiv2020

Environment dependence of rhizobial relative fitness in the legume-rhizobia symbiosis

The environmental context of the nitrogen-fixing mutualism between leguminous plants and rhizobial bacteria varies over space and time. Variation in resource availability, population density, and composition likely affect the ecology and evolution of rhizobia and their symbiotic interactions with hosts. We examined how host genotype, nitrogen addition, rhizobial density, and community complexity affected selection on 68 rhizobia strains in the Ensifer meliloti - Medicago truncatula mutualism. As expected, the host genotype had the most substantial effect on the size, number, and strain composition of root nodules (the symbiotic organ). The understudied environmental variable of rhizobial density had a more significant effect on strain frequency in nodules than the addition of low nitrogen levels. Higher inoculum density resulted in a nodule community that was less diverse and more beneficial but only in the context of the more selective host genotype. Higher density resulted in more diverse and less beneficial nodule communities with the less selective host. Density effects on strain composition deserve additional scrutiny as they can create eco-evolutionary feedback. Lastly, we found that relative strain rankings were stable across increasing community complexity (community complexity (2, 3, 8, or 68 strains). This unexpected result suggests that higher-order interactions between strains are rare in the context of host nodule formation and development. Taken together, our empirical work highlights the importance of developing new theoretical predictions that incorporate density dependence. Further, it has translational relevance for overcoming establishment barriers in bio-inoculants and motivating host breeding programs that maintain beneficial plant-microbe interactions across diverse agro-ecological contexts. IMPORTANCELegume cash, forage, and cover crops establish beneficial associations with rhizobial bacteria who perform biological nitrogen fixation (BNF)--providing Nitrogen (N) fertilizer to plants without the economic and greenhouse gas emission costs of chemical N inputs. Here, for the first time, we examine the relative influence of three environmental factors that vary in agricultural fields on strain relative fitness in nodules when scores rhizobial strains compete. In addition to manipulating Nitrogen, we also use two biotic variables that have rarely been examined: the rhizobial communitys density and complexity. Taken together, our results suggest 1) breeding legume varieties that select beneficial strains despite environmental variation are possible, 2) changes in rhizobial population densities that occur routinely in agricultural fields could drive evolutionary changes in rhizobia populations, and 3) the lack of higher-order interactions between strains will allow the high-throughput assessments of rhizobia winners and losers during plant interactions.

ecology↗