Mx1 -labeled pulp progenitor cells are main contributors to postnatal odontoblasts and pulp cells in murine molars.

Regeneration of dentin and odontoblasts from dental pulp stem cells (DPSCs) is essential for permanent tooth maintenance. However, the in vivo identity and role of endogenous DPSCs in reparative dentinogenesis are elusive. Here, using pulp single-cell analysis before and after molar eruption, we revealed that endogenous DPSCs are enriched in Cxcl12- GFP + coronal papilla-like cells with Mx1- Cre labeling. These Mx1 + Cxcl12- GFP + cells are long-term repopulating cells that contribute to the majority of pulp cells and new odontoblasts after eruption. Upon molar injury, Mx1 + DPSCs localize into the injury site and differentiate into new odontoblasts, forming scleraxis -GFP + and osteocalcin -GFP + dentinal tubules and reparative dentin. Single-cell and FACS analysis showed that Mx1 + Cxcl12- GFP + DPSCs are the most primitive cells with stem cell marker expression and odontoblast differentiation. Taken together, our findings demonstrate that Mx1 labels postnatal DSPCs, which are the main source of pulp cells and new odontoblasts with reparative dentinogenesis in vivo .

Fully reconfigurable MEMS-based second-order coupled-resonator optical waveguide (CROW) with ultra-low tuning energy.

Integrated microring resonators are well suited for wavelength-filtering applications in optical signal processing, and cascaded microring resonators allow flexible filter design in coupled-resonator optical waveguide (CROW) configurations. However, the implementation of high-order cascaded microring resonators with high extinction ratios (ERs) remains challenging owing to stringent fabrication requirements and the need for precise resonator tunability. We present a fully integrated on-chip second-order CROW filter using silicon photonic microelectromechanical systems (MEMS) to adjust tunable directional couplers and a phase shifter using nanoscale mechanical out-of-plane waveguide displacement. The filter can be fully reconfigured with regard to both the ER and center wavelength. We experimentally demonstrated an ER exceeding 25 dB and continuous wavelength tuning across the full free spectral range of 0.123 nm for single microring resonator, and showed reconfigurability in second-order CROW by tuning the ER and resonant wavelength. The tuning energy for an individual silicon photonic MEMS phase shifter or tunable coupler is less than 22 pJ with sub-microwatt static power consumption, which is far better than conventional integrated phase shifters based on other physical modulation mechanisms.

Programmable MZI based on a silicon photonic MEMS-tunable delay line.

We report on a scalable and programmable integrated Mach-Zehnder interferometer (MZI) with a tunable free spectral range (FSR) and extinction ratio (ER). For the tunable path of the MZI, we designed and utilized a tunable delay line having high flexibility based on silicon photonic microelectromechanical systems (MEMS). By utilizing MEMS, the length of the delay line can be geometrically modified. In this way, there is no optical loss penalty other than the waveguide propagation loss as the number of tunable steps increases. Therefore, our device is more scalable in terms of optical loss than the previous approaches based on cascaded MZIs. In addition, the tuning energy required to reconfigure the length is only 8.46 pJ.

Development and Application of a Stability Index Estimation Algorithm Based on Machine Learning for Elderly Balance Ability Diagnosis in Daily Life.

BACKGROUND: The stability index estimation algorithm was derived and applied to develop and implement a balance ability diagnosis system that can be used in daily life. METHODS: The system integrated an approach based on sensory function interaction, called the clinical test of sensory interaction with balance. A capacitance and resistance sensing type force mat was fabricated, and a stability index prediction algorithm was developed and applied using the center of pressure variables. The stability index prediction algorithm derived a center of pressure variable for 103 elderly people by Nintendo Wii Balance Board to predict the stability index of the balance system (Biodex SD), and the accuracy of this approach was confirmed. RESULTS: As a result of testing with the test set, the linear regression model confirmed that the r-value ranged between 0.943 and 0.983. To confirm the similarity between the WBB and the flexible force mat, each measured center of pressure value was inputted and calculated in the developed regression model, and the result of the correlation coefficient validation confirmed an r-value of 0.96. CONCLUSION: The system developed in this study will be applicable to daily life in the home in the form of a floor mat.

Whole-Body Metabolism and the Musculoskeletal Impacts of Targeting Activin A and Myostatin in Severe Osteogenesis Imperfecta.

Mutations in the COL1A1 and COL1A2 genes, which encode type I collagen, are present in around 85%-90% of osteogenesis imperfecta (OI) patients. Because type I collagen is the principal protein composition of bones, any changes in its gene sequences or synthesis can severely affect bone structure. As a result, skeletal deformity and bone frailty are defining characteristics of OI. Homozygous oim/oim mice are utilized as models of severe progressive type III OI. Bone adapts to external forces by altering its mass and architecture. Previous attempts to leverage the relationship between muscle and bone involved using a soluble activin receptor type IIB-mFc (sActRIIB-mFc) fusion protein to lower circulating concentrations of activin A and myostatin. These two proteins are part of the TGF-ß superfamily that regulate muscle and bone function. While this approach resulted in increased muscle masses and enhanced bone properties, adverse effects emerged due to ligand promiscuity, limiting clinical efficacy and obscuring the precise contributions of myostatin and activin A. In this study, we investigated the musculoskeletal and whole-body metabolism effect of treating 5-week-old wildtype (Wt) and oim/oim mice for 11 weeks with either control antibody (Ctrl-Ab) or monoclonal anti-activin A antibody (ActA-Ab), anti-myostatin antibody (Mstn-Ab), or a combination of ActA-Ab and Mstn-Ab (Combo). We demonstrated that ActA-Ab treatment minimally impacts muscle mass in oim/oim mice, whereas Mstn-Ab and Combo treatments substantially increased muscle mass and overall lean mass regardless of genotype and sex. Further, while no improvements in cortical bone microarchitecture were observed with all treatments, minimal improvements in trabecular bone microarchitecture were observed with the Combo treatment in oim/oim mice. Our findings suggest that individual or combinatorial inhibition of myostatin and activin A alone is insufficient to robustly improve femoral biomechanical and microarchitectural properties in severely affected OI mice. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Differential regulation of skeletal stem/progenitor cells in distinct skeletal compartments.

Skeletal stem/progenitor cells (SSPCs), characterized by self-renewal and multipotency, are essential for skeletal development, bone remodeling, and bone repair. These cells have traditionally been known to reside within the bone marrow, but recent studies have identified the presence of distinct SSPC populations in other skeletal compartments such as the growth plate, periosteum, and calvarial sutures. Differences in the cellular and matrix environment of distinct SSPC populations are believed to regulate their stemness and to direct their roles at different stages of development, homeostasis, and regeneration; differences in embryonic origin and adjacent tissue structures also affect SSPC regulation. As these SSPC niches are dynamic and highly specialized, changes under stress conditions and with aging can alter the cellular composition and molecular mechanisms in place, contributing to the dysregulation of local SSPCs and their activity in bone regeneration. Therefore, a better understanding of the different regulatory mechanisms for the distinct SSPCs in each skeletal compartment, and in different conditions, could provide answers to the existing knowledge gap and the impetus for realizing their potential in this biological and medical space. Here, we summarize the current scientific advances made in the study of the differential regulation pathways for distinct SSPCs in different bone compartments. We also discuss the physical, biological, and molecular factors that affect each skeletal compartment niche. Lastly, we look into how aging influences the regenerative capacity of SSPCs. Understanding these regulatory differences can open new avenues for the discovery of novel treatment approaches for calvarial or long bone repair.

Low Power Coherent Ising Machine Based on Mechanical Kerr Nonlinearity.

Finding a reliable Ising machine for solving nondeterministic polynomial-class problems has attracted great attention in recent years, where an authentic system can be expanded with polynomial-scaled resources to find the ground state Ising Hamiltonian. In this Letter, we propose an extremely low power optomechanical coherent Ising machine based on a new enhanced symmetry breaking mechanism and highly nonlinear mechanical Kerr effect. The mechanical movement of an optomechanical actuator induced by the optical gradient force greatly increases the nonlinearity by a few orders and significantly reduces the power threshold using conventional structures capable of fabrication via photonic integrated circuit platforms. With the simple but strong bifurcation mechanism and remarkably low power requirement, our optomechanical spin model opens a path for chip-scale integration of large-size Ising machine implementations with great stability.

Assessment of sources variability of riverine particulate organic matter with land use and rainfall changes using a three-indicator (δ13C, δ15N, and C/N) Bayesian mixing model.

In intensive agricultural watersheds, riverine particulate organic matter (POM) may be transported from many sources such as rice paddies, crop uplands, forests, and livestock farming areas during rainy seasons. However, the impacts of land-use and rainfall changes on the POM sources are not well understood. In this study, changes in the sources of riverine POM were investigated in an agricultural area of Korea between 2014 and 2020/21. During this period, land-use and rainfall patterns changed dramatically. The δ13C, δ15N, and C/N of the POM sources as well as those of riverine POM were analyzed, and a stable isotope analysis in R (SIAR) model was utilized for source apportionment. There were differences in δ13C, δ15N, and C/N among the sources. For example, manure had higher δ13C (-22.6 ± 3.3‰) and δ15N (+10.6 ± 5.9‰) than soils (from -28.0 ± 0.8‰ to -25.1 ± 1.2‰ for δ13C and +3.6 ± 1.7‰ to +9.8 ± 1.4‰ for δ15N). For soils, the δ13C and δ15N were higher for upland soils, while C/N was greater for forest soils than for others. For riverine POM, the δ15N marginally changed; however, the δ13C and C/N increased from -26.1 ± 0.9‰ to -20.8 ± 5.3‰ and from +7.7 ± 1.7 to +18.8 ± 8.3 between 2014 and 2020/21, respectively. The SIAR model showed that the contributions of paddy (from 41.0% to 14.9%) and upland fields (from 48.1% to 23.7%) to riverine POM decreased between the periods due to decreased paddy area and the implementation of best management practice on upland fields, respectively. However, the contribution of forests (from 3.5% to 28.0%) and manure (from 7.4% to 33.5%) increased probably due to improper management of forest clear-cutting sites and livestock manure storage sites. The contributions of agricultural soils to riverine POM decreased in drier years. Our study suggests that land management rather than land-use area is critical in riverine POM management, particularly in wetter years.

Sensory Interaction and Balancing Ability Evaluation of the Elderly Using a Simplified Force Plate System.

The Wii balance board (WBB) is a simplified force plate system used to evaluate the balancing ability of the elderly via a sensory interaction task to confirm a significant standing balance index. The accuracy of this system has been verified in previous studies. In this study, an instrumented and modified clinical test of sensory interaction on balance (i-mCTSIB) was performed on 84 elderly subjects, and the variables for center of pressure (CoP) were calculated using WBB for each task condition. The results indicate that the visual condition has a significant effect on the sway proprioceptive sensory variables with a foam condition as their complexity increases. In addition, the correlation between the variable and Berg Balance Scale was not confirmed since CTSIB is a sensory interaction on balance ability. Therefore, WBB can be used to evaluate balancing ability based on sensory interactions consisting of the surface condition.

Advances and challenges in intravital imaging of craniofacial and dental progenitor cells.

Craniofacial and appendicular bone homeostasis is dynamically regulated by a balance between bone formation and resorption by osteoblasts and osteoclasts, respectively. Despite the developments in multiple imaging techniques in bone biology, there are still technical challenges and limitations in the investigation of spatial/anatomical location of rare stem/progenitor cells and their molecular regulation in tooth and craniofacial bones of living animals. Recent advances in live animal imaging techniques for the craniofacial and dental apparatus can provide new insights in real time into bone stem/progenitor cell dynamics and function in vivo. Here, we review the current inventions and applications of the noninvasive intravital imaging technique and its practical uses and limitations in the analysis of stem/progenitor cells in craniofacial and dental apparatus in vivo. Furthermore, we also explore the potential applications of intravital microscopy in the dental field.

Combinatorial Inhibition of Myostatin and Activin A Improves Femoral Bone Properties in the G610C Mouse Model of Osteogenesis Imperfecta.

Osteogenesis imperfecta (OI) is a collagen-related bone disorder characterized by fragile osteopenic bone and muscle weakness. We have previously shown that the soluble activin receptor type IIB decoy (sActRIIB) molecule increases muscle mass and improves bone strength in the mild to moderate G610C mouse model of OI. The sActRIIB molecule binds multiple transforming growth factor-ß (TGF-ß) ligands, including myostatin and activin A. Here, we investigate the musculoskeletal effects of inhibiting activin A alone, myostatin alone, or both myostatin and activin A in wild-type (Wt) and heterozygous G610C (+/G610C) mice using specific monoclonal antibodies. Male and female Wt and +/G610C mice were treated twice weekly with intraperitoneal injections of monoclonal control antibody (Ctrl-Ab, Regn1945), anti-activin A antibody (ActA-Ab, Regn2476), anti-myostatin antibody (Mstn-Ab, Regn647), or both ActA-Ab and Mstn-Ab (Combo, Regn2476, and Regn647) from 5 to 16 weeks of age. Prior to euthanasia, whole body composition, metabolism and muscle force generation assessments were performed. Post euthanasia, hindlimb muscles were evaluated for mass, and femurs were evaluated for changes in microarchitecture and biomechanical strength using micro-computed tomography (µCT) and three-point bend analyses. ActA-Ab treatment minimally impacted the +/G610C musculoskeleton, and was detrimental to bone strength in male +/G610C mice. Mstn-Ab treatment, as previously reported, resulted in substantial increases in hindlimb muscle weights and overall body weights in Wt and male +/G610C mice, but had minimal skeletal impact in +/G610C mice. Conversely, the Combo treatment outperformed ActA-Ab alone or Mstn-Ab alone, consistently increasing hindlimb muscle and body weights regardless of sex or genotype and improving bone microarchitecture and strength in both male and female +/G610C and Wt mice. Combinatorial inhibition of activin A and myostatin more potently increased muscle mass and bone microarchitecture and strength than either antibody alone, recapturing most of the observed benefits of sActRIIB treatment in +/G610C mice. © 2022 American Society for Bone and Mineral Research (ASBMR).

Biochar-induced reduction of N2O emission from East Asian soils under aerobic conditions: Review and data analysis.

Global meta-analyses showed that biochar application can reduce N2O emission. However, no relevant review study is available for East Asian countries which are responsible for 70% of gaseous N losses from croplands globally. This review analyzed data of the biochar-induced N2O mitigation affected by experimental conditions, including experimental types, biochar types and application rates, soil properties, and chemical forms and application rates of N fertilizer for East Asian countries. The magnitude of biochar-induced N2O mitigation was evaluated by calculating N2O reduction index (Rindex, percentage reduction of N2O by biochar relative to control). The Rindex was further standardized against biochar application rate by calculating Rindex per unit of biochar application rate (ton ha-1) (Unit Rindex). The Rindex averaged across different experimental types (n = 196) was -21.1 ± 2.4%. Incubation and pot experiments showed greater Rindex than column and field experiments due to higher biochar application rate and shorter experiment duration. Feedstock type and pyrolysis temperature also affected Rindex; either bamboo feedstock or pyrolysis at > 400 °C resulted in a greater Rindex. The magnitude of Rindex also increased with increasing biochar rate. Soil properties did not affect Rindex when evaluated across all experimental types, but there was an indication that biochar decreased N2O emission more at a lower soil moisture level in field experiments. The magnitude of Rindex increased with increasing N fertilizer rate up to 500-600 kg N ha-1, but it decreased thereafter. The Unit Rindex averaged across experimental types was -1.2 ± 0.9%, and it was rarely affected by experimental type and conditions but diminished with increasing biochar rate. Our results highlight that since N2O mitigation by biochar is affected by biochar application rate, Rindex needs to be carefully evaluated by standardizing against biochar application rate to suggest the best conditions for biochar usage in East Asia.

Cascaded optical resonator-based programmable photonic integrated circuits.

Programmable photonic integrated circuits have mainly been developed based on the single wavelength channel operation of fundamental building blocks consisting of Mach-Zehnder interferometers (MZIs) with tunable phase shifters. We propose and study optical circuit models consisting of cascaded optical resonators that enable the independent operation of multiple wavelength channels in a more compact footprint than the conventional MZIs. By adopting experimental values reported for silicon micro-ring resonators, the fidelities of different types of 2×2 unitary transformations and higher-dimensional unitary transformations are examined by employing the Reck algorithm and the Clements algorithm.

Rice straw cover decreases soil erosion and sediment-bound C, N, and P losses but increases dissolved organic C export from upland maize fields as evidenced by δ13C.

Soil surface with crop residue is effective in reducing soil erosion and carbon (C), nitrogen (N), and phosphorus (P) losses from sloping fields. However, there is a high possibility that surface cover increases export of dissolved organic C (DOC) though relevant field studies under natural rainfall are lacking. In this study, the effects of surface cover with rice (Oryza sativa L.) straw on soil and CNP losses in both dissolved and sediment-bound forms from maize (Zea mays L.) fields were investigated under two fertilization levels (standard and double) × two types of runoff experiments (natural rainfall and artificial irrigation). Changes in soil properties including moisture, temperature, nutrients, and C concentration as well as maize yield were also examined. Surface cover decreased soil and total CNP losses by up to 82% across the experimental plots with some exceptions. However, surface cover increased DOC export in both natural (by 68-82% in total across all events) and artificial (by 3-4 fold) runoff, suggesting that crop residue cover may act as a DOC pollution source of water bodies. The contribution of rice straw to DOC, which was calculated using the δ13C of DOC from covered plots (-24.1 to -28.0‰) and control plots (-19.6 to -25.1‰), was 52.5-95.8%. The concentrations of K2SO4-extractable and microbial biomass C of the soils did not differ between covered and control plots, suggesting that DOC produced from rice straw was not incorporated into the soils, but rather, was washed out with surface runoff in this study. Surface cover increased maize growth and yield, particularly in double fertilization plots, through improved soil moisture, temperature, and nutrient conditions. To take full advantage of surface cover with crop residue, a further study on reducing DOC loss from crop residue needs to be conducted.

Impact of Genetic and Pharmacologic Inhibition of Myostatin in a Murine Model of Osteogenesis Imperfecta.

Osteogenesis imperfecta (OI) is a genetic connective tissue disorder characterized by compromised skeletal integrity, altered microarchitecture, and bone fragility. Current OI treatment strategies focus on bone antiresorptives and surgical intervention with limited effectiveness, and thus identifying alternative therapeutic options remains critical. Muscle is an important stimulus for bone formation. Myostatin, a TGF-ß superfamily myokine, acts through ActRIIB to negatively regulate muscle growth. Recent studies demonstrated the potential benefit of myostatin inhibition with the soluble ActRIIB fusion protein on skeletal properties, although various OI mouse models exhibited variable skeletal responses. The genetic and clinical heterogeneity associated with OI, the lack of specificity of the ActRIIB decoy molecule for myostatin alone, and adverse events in human clinical trials further the need to clarify myostatin's therapeutic potential and role in skeletal integrity. In this study, we determined musculoskeletal outcomes of genetic myostatin deficiency and postnatal pharmacological myostatin inhibition by a monoclonal anti-myostatin antibody (Regn647) in the G610C mouse, a model of mild-moderate type I/IV human OI. In the postnatal study, 5-week-old wild-type and +/G610C male and female littermates were treated with Regn647 or a control antibody for 11 weeks or for 7 weeks followed by a 4-week treatment holiday. Inhibition of myostatin, whether genetically or pharmacologically, increased muscle mass regardless of OI genotype, although to varying degrees. Genetic myostatin deficiency increased hindlimb muscle weights by 6.9% to 34.4%, whereas pharmacological inhibition increased them by 13.5% to 29.6%. Female +/mstn +/G610C (Dbl.Het) mice tended to have similar trabecular and cortical bone parameters as Wt showing reversal of +/G610C characteristics but with minimal effect of +/mstn occurring in male mice. Pharmacologic myostatin inhibition failed to improve skeletal bone properties of male or female +/G610C mice, although skeletal microarchitectural and biomechanical improvements were observed in male wild-type mice. Four-week treatment holiday did not alter skeletal outcomes. © 2020 American Society for Bone and Mineral Research (ASBMR).

Interferon Gamma Mediates Hematopoietic Stem Cell Activation and Niche Relocalization through BST2.

During chronic infection, the inflammatory cytokine interferon gamma (IFNγ) damages hematopoietic stem cells (HSCs) by disrupting quiescence and promoting excessive terminal differentiation. However, the mechanism by which IFNγ hinders HSC quiescence remains undefined. Using intravital 3-dimensional microscopy, we find that IFNγ disrupts the normally close interaction between HSCs and CXCL12-abundant reticular (CAR) cells in the HSC niche. IFNγ stimulation increases expression of the cell surface protein BST2, which we find is required for IFNγ-dependent HSC relocalization and activation. IFNγ stimulation of HSCs increases their E-selectin binding by BST2 and homing to the bone marrow, which depends on E-selectin binding. Upon chronic infection, HSCs from mice lacking BST2 are more quiescent and more resistant to depletion than HSCs from wild-type mice. Overall, this study defines a critical mechanism by which IFNγ promotes niche relocalization and activation in response to inflammatory stimulation and identifies BST2 as a key regulator of HSC quiescence. VIDEO ABSTRACT.

Real-Time Imaging of CCL5-Induced Migration of Periosteal Skeletal Stem Cells in Mice.

Periosteal skeletal stem cells (P-SSCs) are essential for lifelong bone maintenance and repair, making them an ideal focus for the development of therapies to enhance fracture healing.  Periosteal cells rapidly migrate to an injury to supply new chondrocytes and osteoblasts for fracture healing. Traditionally, the efficacy of a cytokine to induce cell migration has only been conducted in vitro by performing a transwell or scratch assay. With advancements in intravital microscopy using multiphoton excitation, it was recently discovered that 1) P-SSCs express the migratory gene CCR5 and 2) treatment with the CCR5 ligand known as CCL5 improves fracture healing and the migration of P-SSCs in response to CCL5. These results have been captured in real-time. Described here is a protocol to visualize P-SSC migration from the calvarial suture skeletal stem cell (SSC) niche towards an injury after treatment with CCL5. The protocol details the construction of a mouse restraint and imaging mount, surgical preparation of the mouse calvaria, induction of a calvaria defect, and acquisition of time-lapse imaging.

Identification of Functionally Distinct Mx1+αSMA+ Periosteal Skeletal Stem Cells.

The periosteum is critical for bone maintenance and healing. However, the in vivo identity and specific regulatory mechanisms of adult periosteum-resident skeletal stem cells are unknown. Here, we report animal models that selectively and durably label postnatal Mx1+αSMA+ periosteal stem cells (P-SSCs) and establish that P-SSCs are a long-term repopulating, functionally distinct SSC subset responsible for lifelong generation of periosteal osteoblasts. P-SSCs rapidly migrate toward an injury site, supply osteoblasts and chondrocytes, and recover new periosteum. Notably, P-SSCs specifically express CCL5 receptors, CCR3 and CCR5. Real-time intravital imaging revealed that the treatment with CCL5 induces P-SSC migration in vivo and bone healing, while CCL5/CCR5 deletion, CCR5 inhibition, or local P-SSC ablation reduces osteoblast number and delays bone healing. Human periosteal cells express CCR5 and undergo CCL5-mediated migration. Thus, the adult periosteum maintains genetically distinct SSC subsets with a CCL5-dependent migratory mechanism required for bone maintenance and injury repair.

Compromised Exercise Capacity and Mitochondrial Dysfunction in the Osteogenesis Imperfecta Murine (oim) Mouse Model.

Osteogenesis imperfecta (OI) is a heritable connective tissue disorder that most often arises from type I collagen-COL1A1 and COL1A2-gene defects leading to skeletal fragility, short stature, blue-gray sclera, and muscle weakness. Relative to the skeletal fragility, muscle weakness is much less understood. Recent investigations into OI muscle weakness in both patients and mouse models have revealed the presence of an inherent muscle pathology. Understanding the mechanisms responsible for OI muscle weakness is critical, particularly in light of the extensive cross-talk between muscle and bone via mechanotransduction and biochemical signaling. In the following study we initially subjected WT and oim/oim mice, modeling severe human OI type III, to either weight-bearing (voluntary wheel-running) or non-weight-bearing (swimming) exercise regimens as a modality to improve muscle strength and ultimately bone strength. The oim/oim mice ran only 35% to 42% of the distance run by age- and sex-matched WT mice and exhibited little improvement with either exercise regimen. Upon further investigation, we determined that oim/oim gastrocnemius muscle exhibited severe mitochondrial dysfunction as characterized by a 52% to 65% decrease in mitochondrial respiration rates, alterations in markers of mitochondrial biogenesis, mitophagy, and the electron transport chain components, as well as decreased mitochondrial citrate synthase activity, relative to age- and sex-matched WT gastrocnemius muscle. Thus, mitochondrial dysfunction in the oim/oim mouse likely contributes to compromised muscle function and reduced physical activity levels. © 2019 American Society for Bone and Mineral Research.