Chronic intermittent hypobaric hypoxia ameliorates osteoporosis after spinal cord injury through balancing osteoblast and osteoclast activities in rats

Zhang, Li; Yin, Yingchao; Guo, Jialiang; Lin, Jianhao; Hou, Zhiyong

doi:10.3389/fendo.2023.1035186

Cited by 3 publications

(1 citation statement)

References 53 publications

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“…Due to osteopenia after SCI, bone fractures are extremely common in individuals with SCI, because of their lower osteogenic load and increased bone demineralization [ 15 , 16 , 17 ]. The absolute causes of bone loss after SCI are not yet known; however, some of the possible causes are neurogenic factors, hormonal factors, and sarcopenia [ 15 , 18 ]. Immobility and disuse are other causes of osteopenia and sarcopenia in SCI patients due to the decrease in mechanical loading in the bone while one recovers from SCI.…”

Section: Introductionmentioning

confidence: 99%

Rehabilitation: Neurogenic Bone Loss after Spinal Cord Injury

Leone,

Shields,

Haque

et al. 2023

Biomedicines

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Osteoporosis is a common skeletal disorder which can severely limit one’s ability to complete daily tasks due to the increased risk of bone fractures, reducing quality of life. Spinal cord injury (SCI) can also result in osteoporosis and sarcopenia. Most individuals experience sarcopenia and osteoporosis due to advancing age; however, individuals with SCI experience more rapid and debilitating levels of muscle and bone loss due to neurogenic factors, musculoskeletal disuse, and cellular/molecular events. Thus, preserving and maintaining bone mass after SCI is crucial to decreasing the risk of fragility and fracture in vulnerable SCI populations. Recent studies have provided an improved understanding of the pathophysiology and risk factors related to musculoskeletal loss after SCI. Pharmacological and non-pharmacological therapies have also provided for the reduction in or elimination of neurogenic bone loss after SCI. This review article will discuss the pathophysiology and risk factors of muscle and bone loss after SCI, including the mechanisms that may lead to muscle and bone loss after SCI. This review will also focus on current and future pharmacological and non-pharmacological therapies for reducing or eliminating neurogenic bone loss following SCI.

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Section: Introductionmentioning

confidence: 99%

Rehabilitation: Neurogenic Bone Loss after Spinal Cord Injury

Leone,

Shields,

Haque

et al. 2023

Biomedicines

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Beyond resorption: osteoclasts as drivers of bone formation

Xiang,

Li,

et al. 2024

Cell Regen

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Emerging evidence illustrates that osteoclasts (OCs) play diverse roles beyond bone resorption, contributing significantly to bone formation and regeneration. Despite this, OCs remain mysterious cells, with aspects of their lifespan—from origin, fusion, alterations in cellular characteristics, to functions—remaining incompletely understood. Recent studies have identified that embryonic osteoclastogenesis is primarily driven by osteoclast precursors (OCPs) derived from erythromyeloid progenitors (EMPs). These precursor cells subsequently fuse into OCs essential for normal bone development and repair. Postnatally, hematopoietic stem cells (HSCs) become the primary source of OCs, gradually replacing EMP-derived OCs and assuming functional roles in adulthood. The absence of OCs during bone development results in bone structure malformation, including abnormal bone marrow cavity formation and shorter long bones. Additionally, OCs are reported to have intimate interactions with blood vessels, influencing bone formation and repair through angiogenesis regulation. Upon biomaterial implantation, activation of the innate immune system ensues immediately. OCs, originating from macrophages, closely interact with the immune system. Furthermore, evidence from material-induced bone formation events suggests that OCs are pivotal in these de novo bone formation processes. Nevertheless, achieving a pure OC culture remains challenging, and interpreting OC functions in vivo faces difficulties due to the presence of other multinucleated cells around bone-forming biomaterials. We here describe the fusion characteristics of OCPs and summarize reliable markers and morphological changes in OCs during their fusion process, providing guidance for researchers in identifying OCs both in vitro and in vivo. This review focuses on OC formation, characterization, and the roles of OCs beyond resorption in various bone pathophysiological processes. Finally, therapeutic strategies targeting OCs are discussed.

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Combined Effects of Cyclic Hypoxic and Mechanical Stimuli on Human Bone Marrow Mesenchymal Stem Cell Differentiation: A New Approach to the Treatment of Bone Loss

Camacho-Cardenosa,

Pulido-Escribano,

Torrecillas-Baena

et al. 2024

JCM

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Background: The prevention and treatment of bone loss and osteoporotic fractures is a public health challenge. Combined with normobaric hypoxia, whole-body vibration has a high clinic potential in bone health and body composition. The effect of this therapy may be mediated by its action on bone marrow mesenchymal stem cells (MSCs). Objectives: Evaluate the effects of cyclic low-vibration stimuli and/or hypoxia on bone marrow-derived human MSC differentiation. Methods: MSCs were exposed four days per week, two hours/day, to hypoxia (3% O2) and/or vibration before they were induced to differentiate or during differentiation into osteoblasts or adipocytes. Gene and protein expression of osteoblastic, adipogenic, and cytoskeletal markers were studied, as well as extracellular matrix mineralization and lipid accumulation. Results: early osteoblastic markers increased in undifferentiated MSCs, pretreated in hypoxia and vibration. This pretreatment also increased mRNA levels of osteoblastic genes and beta-catenin protein in the early stages of differentiation into osteoblasts without increasing mineralization. When MSCs were exposed to vibration under hypoxia or normoxia during osteoblastic differentiation, mineralization increased with respect to cultures without vibrational stimuli. In MSCs differentiated into adipocytes, both in those pretreated as well as exposed to different conditions during differentiation, lipid formation decreased. Changes in adipogenic gene expression and increased beta-catenin protein were observed in cultures treated during differentiation. Conclusions: Exposure to cyclic hypoxia in combination with low-intensity vibratory stimuli had positive effects on osteoblastic differentiation and negative ones on adipogenesis of bone marrow-derived MSCs. These results suggest that in elderly or frail people with difficulty performing physical activity, exposure to normobaric cyclic hypoxia and low-density vibratory stimuli could improve bone metabolism and health.

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Chronic intermittent hypobaric hypoxia ameliorates osteoporosis after spinal cord injury through balancing osteoblast and osteoclast activities in rats

Cited by 3 publications

References 53 publications

Rehabilitation: Neurogenic Bone Loss after Spinal Cord Injury

Rehabilitation: Neurogenic Bone Loss after Spinal Cord Injury

Beyond resorption: osteoclasts as drivers of bone formation

Combined Effects of Cyclic Hypoxic and Mechanical Stimuli on Human Bone Marrow Mesenchymal Stem Cell Differentiation: A New Approach to the Treatment of Bone Loss

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