Inflammation, ageing, and bone regeneration

Gibon, Emmanuel; Lu, Laura; Nathan, Karthik; Goodman, Stuart B.

doi:10.1016/j.jot.2017.04.002

Cited by 99 publications

(83 citation statements)

References 87 publications

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“…Similarly, additional work is needed to clarify the impact of bone–muscle interactions on bone metabolism in response to various interventions, either pharmacological‐ or exercise‐based. Similarly, our findings suggest that bone‐regenerative capacity may be blunted in older individuals, as has been reported in the general population …”

Section: Discussionsupporting

confidence: 89%

“…Similarly, our findings suggest that bone-regenerative capacity may be blunted in older individuals, as has been reported in the general population. (34)(35)(36) To our knowledge, this is the first study to detail the effects of combining bisphosphonate therapy with a bone-forming stimulus, such as FES-rowing, on bone following SCI. ZA is an antiresorptive therapy and FES-rowing is thought to be an osteogenic stimulus.…”

Section: Discussionmentioning

confidence: 99%

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Combination Therapy With Zoledronic Acid and FES‐Row Training Mitigates Bone Loss in Paralyzed Legs: Results of a Randomized Comparative Clinical Trial

et al. 2019

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Spinal cord injury (SCI) results in rapid, severe osteoporosis and an increased risk of lower extremity fractures. Despite the medical complications associated with these fractures, there is no standard of care to prevent osteoporotic fractures following SCI. Functional electrical stimulation‐ (FES‐) assisted rowing is a promising intervention to improve bone health in SCI because of its ability to generate a muscular contraction in conjunction with mechanical loading of the lower extremity long bones. Combination therapy consisting of FES‐rowing plus zoledronic acid (ZA) may be a superior treatment via inhibition of bone resorption and stimulation of new bone formation. We studied participants enrolled in a randomized clinical trial comparing FES‐rowing alone with FES‐rowing plus ZA to improve bone health in SCI. Volumetric CT scans at the distal femur and proximal tibial metaphyses were performed. Bone geometric properties (cortical thickness index [CTI], cortical compressive strength index [CSI], buckling ratio [BR], bending strength index) and mineral (cortical bone volume [CBV], cortical bone mineral density, cortical bone mineral content) indices were determined. In models adjusting for baseline values, we found that the CBV ( p = 0.05 to 0.006), the CTI ( p = 0.009), and the BR ( p = 0.001) at both the distal femoral and proximal tibial metaphyses were greater in the ZA plus rowing group compared with the rowing‐only group. Similarly, there was a significant positive association between the total rowing work completed and the BR at the proximal tibia ( p = 0.05). A subgroup analysis of the rowing‐only arm showed that gains in the CSI at the tibial metaphysis varied in a dose‐dependent fashion based on the total amount of exercise performed ( p = 0.009). These findings demonstrate that the osteogenic response to FES‐rowing is dose‐dependent. Combination therapy with ZA and FES‐row training has therapeutic potential to improve bone quality, and perhaps reduce fracture risk at the most common fracture site following SCI. © 2019 The Authors. JBMR Plus Published by Wiley Periodicals, Inc. on behalf of the American Society for Bone and Mineral Research.

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Section: Discussionsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 99%

Combination Therapy With Zoledronic Acid and FES‐Row Training Mitigates Bone Loss in Paralyzed Legs: Results of a Randomized Comparative Clinical Trial

et al. 2019

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“…Some studies indicate that inflammatory cytokines peak within the first 24 hr after injury and gradually decline within 7 days (Einhorn & Gerstenfeld, ). However, prolonged or aberrant activation of immune cells or secretion of proinflammatory molecules is detrimental to bone regeneration (Gibon, Lu, Nathan, & Goodman, ). Macrophages are some of the most important immune cells that secrete inflammatory and chemotactic mediators that initiate the recruitment of mesenchymal stem/stromal cells (MSCs) from local niches, such as bone marrow and periosteum (Loi et al, ).…”

Section: Introductionmentioning

confidence: 99%

Immunoregulatory role of exosomes derived from differentiating mesenchymal stromal cells on inflammation and osteogenesis

Wei

Crawford

et al. 2019

J Tissue Eng Regen Med

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Bone marrow-derived mesenchymal stem/stromal cells (BMSCs) can differentiate into bone-forming osteoblasts, playing a crucial role in bone regeneration. Exosomes are naturally cell-secreted nanovesicles and are lately regraded as an emerging mediator of cellular communication in physiological and pathological conditions. The present study aimed at investigating the complex cellular communications, especially those among the differentiating BMSCs, immune cells (e.g., macrophages), and newly recruited BMSCs via exosome-mediated pathways. Exosomes were first isolated from osteogenically differentiating BMSCs at various stages (Day 0, Day 3, Day 7, and Day 14, respectively). The cellular uptake of isolated exosomes was examined in macrophages and human BMSCs (hBMSCs). The exosomes collected at various osteogenic differentiation stages (0d-exo, 3d-exo, 7d-exo, and 14d-exo) had no effect on the viability of hBMSCs. The uptake of exosomes (0d-exo, 3d-exo, and 7d-exo) significantly decreased proinflammatory-gene expression and the level of an M1 phenotypic marker. Our results then revealed that 3d-exo, 7d-exo, and 14d-exo led to a remarkable increase in mesenchymal stem/stromal cell migration. In addition, 0d-exo significantly promoted the expression of early osteogenic markers, such as alkaline phosphatase and bone morphogenetic protein 2, indicating a pro-osteogenic role of hBMSC-derived exosomes. Collectively, these results suggest that exosomes derived from differentiating mesenchymal stem/stromal cells play a unique osteoimmunomodulatory role in the regulation of bone dynamics.

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“…Bone fracture healing can be described in three characteristic phases: Inflammatory, repair, and remodelling (see Figure 1) [24]. During inflammation, necroses of cells result in the delivery of pro-inflammatory cytokines which attract inflammatory immune cells, such as neutrophils and monocytes [1,23], to the injury site.…”

Section: Biological Backgroundmentioning

confidence: 99%

Modeling the Macrophage-Mediated Inflammation Involved in the Bone Fracture Healing Process

Trejo

Kojouharov

Chen-Charpentier

2019

MCA

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A new mathematical model is presented to study the effects of macrophages on the bone fracture healing process. The model consists of a system of nonlinear ordinary differential equations that represents the interactions among classically and alternatively activated macrophages, mesenchymal stem cells, osteoblasts, and pro- and anti-inflammatory cytokines. A qualitative analysis of the model is performed to determine the equilibria and their corresponding stability properties. Numerical simulations are also presented to support the theoretical results, and to monitor the evolution of a broken bone for different types of fractures under various medical interventions. The model can be used to guide clinical experiments and to explore possible medical treatments that accelerate the bone fracture healing process, either by surgical interventions or drug administrations.

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Inflammation, ageing, and bone regeneration

Cited by 99 publications

References 87 publications

Combination Therapy With Zoledronic Acid and FES‐Row Training Mitigates Bone Loss in Paralyzed Legs: Results of a Randomized Comparative Clinical Trial

Combination Therapy With Zoledronic Acid and FES‐Row Training Mitigates Bone Loss in Paralyzed Legs: Results of a Randomized Comparative Clinical Trial

Immunoregulatory role of exosomes derived from differentiating mesenchymal stromal cells on inflammation and osteogenesis

Modeling the Macrophage-Mediated Inflammation Involved in the Bone Fracture Healing Process

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