Traumatic brain injury enhances the formation of heterotopic ossification around the hip: an animal model study

Anthonissen, Joris; Steffen, Clara Theressa; Alessandri, B.; Baranowski, Andreas; Rommens, Pol Maria; Victor, Jan; Hofmann, Alexander

doi:10.1007/s00402-019-03326-0

Cited by 17 publications

(13 citation statements)

References 27 publications

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“…Although it has been agreed that neurological HO, initiated by simultaneous central and peripheral nervous injury, represents endochondral ossification, the underlying molecular and cellular mechanisms still remain to be elucidated [ 122 , 124 , 125 ]. Recently established TBI models sustaining HO potentially provide the foundation for investigations of the pathogenesis while unraveling promising therapeutic targets [ 126 , 127 ].…”

Section: Clinical Observationsmentioning

confidence: 99%

Crosstalk of Brain and Bone—Clinical Observations and Their Molecular Bases

Otto

Knapstein

Jahn

et al. 2020

IJMS

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As brain and bone disorders represent major health issues worldwide, substantial clinical investigations demonstrated a bidirectional crosstalk on several levels, mechanistically linking both apparently unrelated organs. While multiple stress, mood and neurodegenerative brain disorders are associated with osteoporosis, rare genetic skeletal diseases display impaired brain development and function. Along with brain and bone pathologies, particularly trauma events highlight the strong interaction of both organs. This review summarizes clinical and experimental observations reported for the crosstalk of brain and bone, followed by a detailed overview of their molecular bases. While brain-derived molecules affecting bone include central regulators, transmitters of the sympathetic, parasympathetic and sensory nervous system, bone-derived mediators altering brain function are released from bone cells and the bone marrow. Although the main pathways of the brain-bone crosstalk remain ‘efferent’, signaling from brain to bone, this review emphasizes the emergence of bone as a crucial ‘afferent’ regulator of cerebral development, function and pathophysiology. Therefore, unraveling the physiological and pathological bases of brain-bone interactions revealed promising pharmacologic targets and novel treatment strategies promoting concurrent brain and bone recovery.

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Section: Clinical Observationsmentioning

confidence: 99%

Crosstalk of Brain and Bone—Clinical Observations and Their Molecular Bases

Otto

Knapstein

Jahn

et al. 2020

IJMS

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“…In fracture patients concurrently affected by TBIs, the interplay between bone fracture and TBI creates a complex relationship that deserves exploration. TBI‐induced perturbations in cellular and molecular cascades may inadvertently predispose individuals to HO development at sites other than the primary fracture site [65,66] . These ectopic ossifications can potentially disrupt the orchestrated healing cascade, impeding the restoration of normal anatomical and functional integrity.…”

Section: Endocrine Factors and Neuropeptides In Tbi‐enhanced Bone Hea...mentioning

confidence: 99%

“…However, the relationship between TBIs and HO in the context of fracture healing is multifaceted and not fully elucidated. The occurrence of HO in concurrent TBI and fracture patients may depend on various factors, including TBI severity, fracture site, and individual characteristics [65–67] …”

Section: Endocrine Factors and Neuropeptides In Tbi‐enhanced Bone Hea...mentioning

confidence: 99%

The mechanism of bone healing after traumatic brain injury

Xiong,

Zhong,

2023

Brain-X

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A growing body of evidence suggests that patients who experience traumatic brain injuries (TBIs) exhibit significantly shorter healing periods compared to those with isolated fractures. However, the precise underlying mechanism behind this phenomenon remains unclear. Recent studies have shed light on the potential role of hormonal signals and neural circuits originating in the hypothalamus, which play vital roles in regulating the skeletal system. Despite these advances, there is a lack of comprehensive research summarizing the crucial role of bone healing in TBIs and the underlying mechanisms. This review aimed to explore the underlying mechanisms responsible for the accelerated bone healing observed in TBI patients, with a specific focus on the intricate crosstalk between TBI and bone remodeling. Additionally, we comprehensively discuss and summarize the beneficial effects of TBI on the skeletal system and examine the TBI‐induced signaling pathways that result in accelerated fracture healing and bone remodeling. By dissecting these pathways, we aim to identify potential targets for intervention and bone repair promotion.

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“…Despite the diversity of stimulus that cause HO, it has been reported that the osteogenic signals remained greatly elevated during HO progression and committed progenitor cells to enhanced osteogenic behavior 8,9 . In the studies incorporating brain‐trauma or burn‐injury into animal models that recapitulate the trauma‐induced HO, the osteogenic activities of relevant progenitor cells can even be further reinforced by these concomitant injuries that are clinically relevant in the context of HO formation 10,11 . Nonetheless, virtually all evidences were obtained on the basis of rodent models, while there could be huge disparities between pathogenesis of rodent and human.…”

Section: Introductionmentioning

confidence: 99%

“…8,9 In the studies incorporating brain-trauma or burn-injury into animal models that recapitulate the trauma-induced HO, the osteogenic activities of relevant progenitor cells can even be further reinforced by these concomitant injuries that are clinically relevant in the context of HO formation. 10,11 Nonetheless, virtually all evidences were obtained on the basis of rodent models, while there could be huge disparities between pathogenesis of rodent and human. Thus, these prior findings may not exactly reflect the real clinical scenarios.…”

Section: Introductionmentioning

confidence: 99%

Human osteoprogenitor cells obtained from traumatic heterotopic ossification samples showed enhanced osteogenic differentiation potential and ERK/hedgehog signaling than that from normal bone

Zhang

Sun

et al. 2022

IUBMB Life

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Traumatic heterotopic ossification (HO) refers to the abnormal ectopic osteogenesis following trauma, causing limb dysfunction and seriously lowering the life quality of patients. Aberrant osteogenic behavior of progenitor cells that ectopically accumulated within the soft tissues are believed to be responsible for HO formation. However, the detailed mechanism still remained to be clarified. Here in this study, we successfully isolated osteoprogenitors from human heterotopic ossification tissues (HO-ops) and identified their stemness and multi-directional differentiation potential. Using alkaline phosphatase staining together with alizarin red staining, we confirmed that the HO-ops in the heterotopic ossified tissues gained greater osteogenic potential than the normal human bone marrow mesenchymal stem cells (HBMSCs). RT-qPCR also indicated that HO-ops obtained more gene transcriptions of critical osteogenic determinators than HBMSCs. In addition, through Western blot, we proved that ERK signaling pathway and hedgehog signaling pathway were significantly activated in the HO-ops. When U0126 and cyclopamine were used to inhibit ERK signaling and hedgehog signaling respectively, the osteogenic potential of HO-ops decreased significantly. The hedgehog signaling and ERK signaling also showed cross-talk in HO-ops during osteogenic differentiation in HO-ops during osteogenic differentiation. The elevated ERK signaling and hedgehog signaling were further confirmed in the human traumatic HO

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Traumatic brain injury enhances the formation of heterotopic ossification around the hip: an animal model study

Cited by 17 publications

References 27 publications

Crosstalk of Brain and Bone—Clinical Observations and Their Molecular Bases

Crosstalk of Brain and Bone—Clinical Observations and Their Molecular Bases

The mechanism of bone healing after traumatic brain injury

Human osteoprogenitor cells obtained from traumatic heterotopic ossification samples showed enhanced osteogenic differentiation potential and ERK/hedgehog signaling than that from normal bone

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