Evaluation of Salivary Cytokines for Diagnosis of both Trauma-Induced and Genetic Heterotopic Ossification

Hsieh, Hsiao Hsin Sung; Chung, Michael T.; Allen, Ronald M.; Ranganathan, Kavitha; Habbouche, Joe; Cholok, David; Butts, Jonathan; Kaura, Arminder; Tiruvannamalai-Annamalai, Ramkumar; Breuler, Chris; Priest, Caitlin; Loder, Shawn; Li, John; Li, Shuli; Stegemann, Jan P.; Kunkel, Steven L.; Lévi, Benjamin

doi:10.3389/fendo.2017.00074

Cited by 33 publications

(23 citation statements)

References 48 publications

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“…Concentrations of IL-1β remained unchanged, while IL-6 and TNFα were undetectable; this may reflect the nature of the intervention, as impact on these pro-inflammatory cytokines varies greatly with exercise duration and intensity [13]. Recent studies indicate that levels of salivary cytokines can be correlated to those found in serum in some disease models [35]. It is worth emphasizing again that our sample was young, active and healthy, thus, results may be of even greater magnitude among those at risk or with existing chronic conditions associated with low-grade systemic inflammation.…”

Section: Discussionmentioning

confidence: 99%

Disrupting prolonged sitting reduces IL-8 and lower leg swell in active young adults

Dogra

Wolf

Jeffrey

et al. 2019

BMC Sports Sci Med Rehabil

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Background Evidence suggests that disrupting prolonged bouts of sitting with short bouts of physical activity can significantly reduce blood glucose and improve insulin sensitivity; however, limited research is available on the impact of such disruptions on inflammation and swelling. The purpose of this study was to determine whether short bouts of exercise performed each hour during a 4 h sitting session were able to negate the effects of prolonged sitting (PS) on several cardiometabolic outcomes. Methods Eligible participants (n = 10) attended two laboratory sessions: PS (uninterrupted sitting for 4 h) and disrupted sitting (DS; 4 h sitting session disrupted by 3 min of exercise each hour (60-s warm-up at 50 W, 5 s of unloaded cycling, 20-s sprint at 5% body weight, and 95-s cool-down at 50 W)). The exercise bouts were performed at minute 60, 120, and 180. Blood and saliva samples, and measures of heart rate and blood pressure were assessed before (T1) and after (T2) each session; leg swell was measured continuously. Results Concentrations of salivary IL-8 increased during PS (T1: 0.19 ± 0.32; T2: 0.50 ± 1.00 pg/μg of protein) but decreased during DS (T1: 0.41 ± 0.23; T2: 0.22 ± 0.11 pg/μg of protein, d: 0.51, p = 0.002). Leg swell increased and plateaued in PS, but was attenuated during DS. Conclusion It appears that short bouts of exercise significantly reduce swelling in the lower leg and IL-8 levels in the saliva, indicating that even among healthy, active, young adults, disrupting prolonged sitting can significantly reduce swelling and systemic inflammation.

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Section: Discussionmentioning

confidence: 99%

Disrupting prolonged sitting reduces IL-8 and lower leg swell in active young adults

Dogra

Wolf

Jeffrey

et al. 2019

BMC Sports Sci Med Rehabil

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“…Previous lineage tracing demonstrated that many mesenchymal stem/progenitor subpopulations, including Prx-cre [28], Scleraxis-cre [29], Nfatc1-cre [30], MX1-cre [31], and Wnt1-cre [32], in addition to the three subpopulations (Tie2-cre, Gli1-creER, and Glast-creERT) we have tested in this study, contribute significantly to HO [13–15, 31]. A key question in this study was whether these subpopulations contribute to HO through the MSC niche.…”

Section: Discussionmentioning

confidence: 99%

BMP-dependent, injury-induced stem cell niche as a mechanism of heterotopic ossification

et al. 2019

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BackgroundHeterotopic ossification (HO), either acquired (aHO) or hereditary, such as fibrodysplasia ossificans progressiva (FOP), is a serious condition without effective treatment. Understanding of the core process of injury-induced HO is still severely limited.MethodsDouble-pulse thymidine analog labeling was used to explore the distinctive domains evolved in injury-induced lesions in an animal model of HO (Nse-BMP4). Histological studies were performed to see whether a similar zonal pattern is also consistently found in biopsies from patients with aHO and FOP. In vivo clonal analysis with Rainbow mice, genetic loss-of-function studies with diphtheria toxin A (DTA)-mediated depletion and lineage tracing with Zsgreen reporter mice were used to obtain further evidence that Tie2-cre-, Gli1-creERT-, and Glast-creERT-labeled cells contribute to HO as niche-dwelling progenitor/stem cells. Immunohistochemistry was used to test whether vasculature, neurites, macrophages, and mast cells are closely associated with the proposed niche and thus are possible candidate niche supportive cells. Similar methods also were employed to further understand the signaling pathways that regulate the niche and the resultant HO.ResultsWe found that distinctive domains evolved in injury-induced lesions, including, from outside-in, a mesenchymal stem cell (MSC) niche, a transient domain and an inner differentiated core in an animal model of HO (Nse-BMP4). A similar zonal structure was found in patients with aHO and FOP. In vivo clonal analysis with Rainbow mice and genetic loss-of-function studies with DTA provided evidence that Tie2-cre-, Gli1-creERT-, and Glast-creERT-labeled cells contribute to HO as niche-dwelling progenitor/stem cells; consistently, vasculature, neurites, macrophages, and mast cells are closely associated with the proposed niche and thus are possible candidate niche supportive cells. Further mechanistic study found that BMP and hedgehog (Hh) signaling co-regulate the niche and the resultant HO.ConclusionsAvailable data provide evidence of a potential core mechanism in which multiple disease-specific cellular and extracellular molecular elements form a unique local microenvironment, i.e., an injury-induced stem cell niche, which regulates the proliferation and osteogenic differentiation of mesenchymal stem cells (MSCs). The implication for HO is that therapeutic approaches must consider several different disease specific factors as parts of a functional unit, instead of treating one factor at a time.Electronic supplementary materialThe online version of this article (10.1186/s13287-018-1107-7) contains supplementary material, which is available to authorized users.

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“…Local wound site expression of these markers as assessed by qPCR was generally found to temporally overlap with rise and fall of detected levels within the serum. (178) Within the same model, increased levels of MCP‐1 were also found in murine saliva, although other assayed markers were too low for detection . Increased inflammatory markers have also been observed among human traumatic HO, both at the local and systemic level.…”

Section: Basic Biologic Features Of Heterotopic Ossificationmentioning

confidence: 94%

“…Correlation of levels of inflammatory cytokines to bone formation is best documented in nongenetic HO. For example, in a mouse model combining cutaneous burn with Achilles tenotomy, increased serum levels of TNFα, IL‐1β, IL‐6, and MCP‐1 were associated with HO formation . Local wound site expression of these markers as assessed by qPCR was generally found to temporally overlap with rise and fall of detected levels within the serum.…”

Section: Basic Biologic Features Of Heterotopic Ossificationmentioning

confidence: 99%

Heterotopic Ossification: A Comprehensive Review

et al. 2019

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Heterotopic ossification (HO) is a diverse pathologic process, defined as the formation of extraskeletal bone in muscle and soft tissues. HO can be conceptualized as a tissue repair process gone awry and is a common complication of trauma and surgery. This comprehensive review seeks to synthesize the clinical, pathoetiologic, and basic biologic features of HO, including nongenetic and genetic forms. First, the clinical features, radiographic appearance, histopathologic diagnosis, and current methods of treatment are discussed. Next, current concepts regarding the mechanistic bases for HO are discussed, including the putative cell types responsible for HO formation, the inflammatory milieu and other prerequisite “niche” factors for HO initiation and propagation, and currently available animal models for the study of HO of this common and potentially devastating condition. © 2019 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.

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Evaluation of Salivary Cytokines for Diagnosis of both Trauma-Induced and Genetic Heterotopic Ossification

Cited by 33 publications

References 48 publications

Disrupting prolonged sitting reduces IL-8 and lower leg swell in active young adults

Disrupting prolonged sitting reduces IL-8 and lower leg swell in active young adults

BMP-dependent, injury-induced stem cell niche as a mechanism of heterotopic ossification

Heterotopic Ossification: A Comprehensive Review

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