A comparison of bone microarchitectural and transcriptomic changes in murine long bones in response to hindlimb unloading and aging

Article Orthopedics

Effects of hindlimb suspension on development of proximal and distal femur morphological abnormalities in growing rats

Junya Ozawa et al.

Summary: This study investigated the effect of hindlimb suspension on femoral morphogenesis in growing rats and found that sufficient physical activity may protect against morphological femur abnormalities.

JOURNAL OF ORTHOPAEDIC RESEARCH (2023)

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Article Multidisciplinary Sciences

Senescence atlas reveals an aged-like inflamed niche that blunts muscle regeneration

Victoria Moiseeva et al.

Summary: This study reveals that senescent cells are crucial components of the skeletal muscle regenerative niche and inhibit regeneration. Through single-cell transcriptomics and senescent-cell enrichment sorting, different types of senescent cells were identified and isolated from damaged muscles of young and old mice. The findings demonstrate that senescent cells create an aged-like inflamed niche and impair stem cell proliferation and regeneration.

NATURE (2023)

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Article Biochemistry & Molecular Biology

YAP Inhibition Alleviates Simulated Microgravity-Induced Mesenchymal Stem Cell Senescence via Targeting Mitochondrial Dysfunction

Wenjun Lv et al.

Summary: Weightlessness in space leads to detrimental effects on astronauts, including bone loss, muscle atrophy, and impaired immune defense. The study investigates the effects of simulated microgravity on mesenchymal stem cells (MSCs) and the potential therapeutic target for weightlessness-related cell senescence and aging. The results suggest that mitochondrial dysfunction mediates MSC senescence induced by simulated microgravity and inhibition of Yes-associated protein (YAP) alleviates MSC senescence through targeting mitochondrial dysfunction.

ANTIOXIDANTS (2023)

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Article Endocrinology & Metabolism

Differential bone adaptation to mechanical unloading and reloading in young, old, and osteocyte deficient mice

Hailey C. Cunningham et al.

Summary: Mechanical unloading causes rapid loss of bone structure and strength, which gradually recovers after resuming normal loading. However, it is not well established how this adaptation to unloading and reloading changes with age. In this study, they examined bone adaptation during unloading and subsequent reloading in mice of different ages, and found important differences in bone adaptation between young and old mice, as well as osteocyte deficient mice. These findings suggest a period of vulnerability in skeletal health in older subjects during and following a period of disuse.

BONE (2023)

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Article Clinical Neurology

In search of stress: analysis of stress-related markers in mice after hindlimb unloading and social isolation

Alexandra A. Naumova et al.

NEUROLOGICAL RESEARCH (2023)

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Article Endocrinology & Metabolism

Reambulation following hindlimb unloading attenuates disuse-induced changes in murine fracture healing

Evan G. Buettmann et al.

Summary: Patients with bone and muscle loss from prolonged disuse have a higher risk of falls and fractures. Fracture patients with continued disuse and delayed rehabilitation have worse clinical outcomes. This study aimed to investigate the effects of prior disuse followed by physical reambulation on fracture healing and recovery. The results suggest that immediate weight-bearing activity following fracture can improve callus healing and prevent further fall risk by stimulating skeletal muscle anabolism and decreasing callus resorption.

BONE (2023)

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Article Biochemistry & Molecular Biology

Dissociation of Bone Resorption and Formation in Spaceflight and Simulated Microgravity: Potential Role of Myokines and Osteokines?

Patrick Lau et al.

Summary: The dissociation of bone formation and resorption is an important physiological process during spaceflight and other special conditions. The interplay between known myokines and osteokines and their mutual regulation is highlighted. However, the long-term changes in bone microarchitecture and the recovery of bone loss in the absence of gravity remain largely unknown.

BIOMEDICINES (2022)

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Review Endocrinology & Metabolism

Similarities Between Disuse and Age-Induced Bone Loss

Evan G. Buettmann et al.

Summary: This article provides an overview of the risk factors associated with low bone mass and quality deterioration due to disuse and aging. It discusses the similarities and differences between bone loss in extreme disuse and advanced aging at various levels, including organ/tissue, cellular, and molecular levels. The shared structural alterations, changes in bone cell function, and potential mechanisms underlying bone loss in both disuse and aging are highlighted. Understanding these similarities and mechanisms is crucial for developing therapies for age-related and disuse-induced osteoporosis.

JOURNAL OF BONE AND MINERAL RESEARCH (2022)

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Article Endocrinology & Metabolism

Cortical bone relationships are maintained regardless of sex and diet in a large population of LGXSM advanced intercross mice

Nicole Migotsky et al.

Summary: This study analyzed the structure-function relationships of long bones in a genetically diverse mouse population. The results showed that there is a moderate correlation between morphological traits of the femur and radius, but weak correlation between mechanical properties and material properties of the two bones. The material properties of the femur are strongly correlated with bone size parameters, while this correlation is very weak in the radius. The study highlights the importance of mechanical testing and the challenges in accurately predicting material properties of the femur.

BONE REPORTS (2022)

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Review Geriatrics & Gerontology

Pathobiology of the Klotho Antiaging Protein and Therapeutic Considerations

Gerald J. Prud'homme et al.

Summary: The Klotho protein has antiaging properties and its levels decline with age and various diseases. Klotho extends lifespan through regulating mineral metabolism, inhibiting age-related pathways, and increasing antioxidant enzymes. Preclinical and clinical studies have shown that increasing Klotho levels can prevent and treat kidney disease, cardiovascular disease, neurodegenerative diseases, and cancer. Drugs, nutraceuticals, and exercise can enhance Klotho levels.

FRONTIERS IN AGING (2022)

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Review Medicine, Research & Experimental

Cellular senescence and the skeleton: pathophysiology and therapeutic implications

Sundeep Khosla et al.

Summary: Cellular senescence is a key mechanism in aging, especially in the skeletal system, and targeting senescent cells shows promise in preventing age-related bone loss and fragility. Efforts are underway to develop senolytic drugs that specifically kill senescent cells while sparing normal cells, offering a potential treatment for multiple age-related comorbidities.

JOURNAL OF CLINICAL INVESTIGATION (2022)

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Article Biochemistry & Molecular Biology

Simulated microgravity accelerates aging of human skeletal muscle myoblasts at the single cell level

Hironobu Takahashi et al.

Summary: Studies on the effects of simulated microgravity on human skeletal muscle myoblasts showed that microgravity accelerates cellular aging, decreases cell proliferation, and enlarges the cytoskeleton and nucleus of cells. These microgravity effects persisted even after the cells returned to normal gravity conditions, leading to reduced capability of differentiation into myotubes.

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS (2021)

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Article Multidisciplinary Sciences

RNAseq and RNA molecular barcoding reveal differential gene expression in cortical bone following hindlimb unloading in female mice

Jordan M. Spatz et al.

Summary: The study reveals potential mechanosensitive genes associated with bone formation after the use of the hindlimb unloading mouse model, suggesting novel targets to prevent disuse-induced osteoporosis.

PLOS ONE (2021)

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Article Endocrinology & Metabolism

Genetic variability affects the skeletal response to immobilization in founder strains of the diversity outbred mouse population

Michael A. Friedman et al.

Summary: Mechanical unloading leads to bone loss, with different inbred mouse strains showing varying responses based on their genetic backgrounds. Gene expression changes in response to unloading, with some strains displaying greater loss in bone mineral density and strength. Diversity outbred (DO) mice may be ideal for further genetic studies on the skeletal response to unloading.

BONE REPORTS (2021)

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Article Endocrinology & Metabolism

Sciatic neurectomy-related cortical bone loss exhibits delayed onset yet stabilises more rapidly than trabecular bone

Samuel Monzem et al.

Summary: Disuse osteoporosis following sciatic neurectomy in mice results in different patterns of bone loss in cortical and trabecular compartments. Trabecular bone volume and number decrease within 5 days, while changes in cortical thickness and structure are significant only after 35 days. Cortical bone loss extends along the entire tibia but stabilizes more rapidly, indicating distinct responses of cortical and trabecular compartments to disuse.

BONE REPORTS (2021)

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Article Biology

p16 deficiency attenuates intervertebral disc degeneration by adjusting oxidative stress and nucleus pulposus cell cycle

Hui Che et al.

ELIFE (2020)

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Review Endocrinology & Metabolism

Osteocyte Cellular Senescence

Joshua N. Farr et al.

CURRENT OSTEOPOROSIS REPORTS (2020)

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Article Multidisciplinary Sciences

Hindlimb unloading causes regional loading-dependent changes in osteocyte inflammatory cytokines that are modulated by exogenous irisin treatment

Corinne E. Metzger et al.

NPJ MICROGRAVITY (2020)

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Article Multidisciplinary Sciences

Mechanical loading recovers bone but not muscle lost during unloading

Andrew R. Krause et al.

NPJ MICROGRAVITY (2020)

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Review Endocrinology & Metabolism

Use it or lose it to age: A review of bone and muscle communication

Lynda Bonewald

BONE (2019)

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Article Biochemistry & Molecular Biology

p16Ink4a deletion in cells of the intervertebral disc affects their matrix homeostasis and senescence associated secretory phenotype without altering onset of senescence

Emanuel J. Novais et al.

MATRIX BIOLOGY (2019)

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Article Orthopedics

Ageing characteristics of bone indicated by transcriptomic and exosomal proteomic analysis of cortical bone cells

Chenyang Zhang et al.

JOURNAL OF ORTHOPAEDIC SURGERY AND RESEARCH (2019)

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Review Oncology

The FGF metabolic axis

Xiaokun Li

FRONTIERS OF MEDICINE (2019)

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Article Behavioral Sciences

Inducing Physical Inactivity in Mice: Preventing Climbing and Reducing Cage Size Negatively Affect Physical Fitness and Body Composition

Peter Roemers et al.

FRONTIERS IN BEHAVIORAL NEUROSCIENCE (2019)

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Article Biophysics

Single limb immobilization model for bone loss from unloading

Michael A. Friedman et al.

JOURNAL OF BIOMECHANICS (2019)

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Article Cell Biology

Elimination of senescent osteoclast progenitors has no effect on the age-associated loss of bone mass in mice

Ha-Neui Kim et al.

AGING CELL (2019)

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Article Orthopedics

Age-dependent bone loss and recovery during hindlimb unloading and subsequent reloading in rats

Hailey C. Cunningham et al.

BMC MUSCULOSKELETAL DISORDERS (2018)

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Review Medicine, Research & Experimental

Role of sphingolipids in senescence: implication in aging and age-related diseases

Magali Trayssac et al.

JOURNAL OF CLINICAL INVESTIGATION (2018)

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Article Multidisciplinary Sciences

Inhibition of interleukin-6 decreases atrogene expression and ameliorates tail suspension-induced skeletal muscle atrophy

Mitsutaka Yakabe et al.

PLOS ONE (2018)

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Article Biochemistry & Molecular Biology

BioJupies: Automated Generation of Interactive Notebooks for RNA-Seq Data Analysis in the Cloud

Denis Torre et al.

CELL SYSTEMS (2018)

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Article Veterinary Sciences

Does age matter? The impact of rodent age on study outcomes

Samuel J. Jackson et al.

LABORATORY ANIMALS (2017)

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Article Biochemistry & Molecular Biology

Targeting cellular senescence prevents age-related bone loss in mice

Joshua N. Farr et al.

NATURE MEDICINE (2017)

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Clustergrammer, a web-based heatmap visualization and analysis tool for high-dimensional biological data

Nicolas F. Fernandez et al.

SCIENTIFIC DATA (2017)

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Review Biochemistry & Molecular Biology

Senescence in Health and Disease

Shenghui He et al.

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Mitochondria are required for pro-ageing features of the senescent phenotype

Clara Correia-Melo et al.

EMBO JOURNAL (2016)

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Osteocyte Apoptosis Caused by Hindlimb Unloading is Required to Trigger Osteocyte RANKL Production and Subsequent Resorption of Cortical and Trabecular Bone in Mice Femurs

Pamela Cabahug-Zuckerman et al.

JOURNAL OF BONE AND MINERAL RESEARCH (2016)

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Identification of Senescent Cells in the Bone Microenvironment

Joshua N. Farr et al.

JOURNAL OF BONE AND MINERAL RESEARCH (2016)

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Article Biochemistry & Molecular Biology

limma powers differential expression analyses for RNA-sequencing and microarray studies

Matthew E. Ritchie et al.

NUCLEIC ACIDS RESEARCH (2015)

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Trabecular bone recovers from mechanical unloading primarily by restoring its mechanical function rather than its morphology

Engin Ozcivici et al.

BONE (2014)

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Connexin 43 deficiency desensitizes bone to the effects of mechanical unloading through modulation of both arms of bone remodeling

Shane A. Lloyd et al.

BONE (2013)

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Constitutive HER2 Signaling Promotes Breast Cancer Metastasis through Cellular Senescence

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CANCER RESEARCH (2013)

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Article Multidisciplinary Sciences

Microgravity Induces Pelvic Bone Loss through Osteoclastic Activity, Osteocytic Osteolysis, and Osteoblastic Cell Cycle Inhibition by CDKN1a/p21

Elizabeth A. Blaber et al.

PLOS ONE (2013)

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Connexin 43 Deficiency Attenuates Loss of Trabecular Bone and Prevents Suppression of Cortical Bone Formation During Unloading

Shane A. Lloyd et al.

JOURNAL OF BONE AND MINERAL RESEARCH (2012)

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Age-Related Changes in Bone Structure and Strength in Female and Male BALB/c Mice

Mark D. Willinghamm et al.

CALCIFIED TISSUE INTERNATIONAL (2010)

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Oncogene-induced senescence relayed by an interleukin-dependent inflammatory network

Thomas Kuilman et al.

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Skeletal involution by age-associated oxidative stress and its acceleration by loss of sex steroids

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JOURNAL OF BIOLOGICAL CHEMISTRY (2007)

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Age-related changes in trabecular architecture differ in female and male C57BL/6J mice

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Osteocyte apoptosis is induced by weightlessness in mice and precedes osteoclast recruitment and bone loss

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C/EBPβ cooperates with RB:E2F to implement RasV12-induced cellular senescence

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Epidemiology and outcomes of osteoporotic fractures

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A comparison of bone microarchitectural and transcriptomic changes in murine long bones in response to hindlimb unloading and aging

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