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(searched for: (title:(Musculoskeletal system for healing of a bone fracture)
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International Journal of Molecular Sciences, Volume 21; doi:10.3390/ijms21072513

Abstract:
Local pH is stated to acidify after bone fracture. However, the time course and degree of acidification remain unknown. Whether the acidification pattern within a fracture hematoma is applicable to adjacent muscle hematoma or is exclusive to this regenerative tissue has not been studied to date. Thus, in this study, we aimed to unravel the extent and pattern of acidification in vivo during the early phase post musculoskeletal injury. Local pH changes after fracture and muscle trauma were measured simultaneously in two pre-clinical animal models (sheep/rats) immediately after and up to 48 h post injury. The rat fracture hematoma was further analyzed histologically and metabolomically. In vivo pH measurements in bone and muscle hematoma revealed a local acidification in both animal models, yielding mean pH values in rats of 6.69 and 6.89, with pronounced intra- and inter-individual differences. The metabolomic analysis of the hematomas indicated a link between reduction in tricarboxylic acid cycle activity and pH, thus, metabolic activity within the injured tissues could be causative for the different pH values. The significant acidification within the early musculoskeletal hematoma could enable the employment of the pH for novel, sought-after treatments that allow for spatially and temporally controlled drug release.
, Lauren H. Mangum, Joseph C. Wenke
Published: 4 June 2020
Frontiers in Immunology, Volume 11; doi:10.3389/fimmu.2020.01056

Abstract:
Single trauma injuries or isolated fractures are often manageable and generally heal without complications. In contrast, high-energy trauma results in multi/poly-trauma injury patterns presenting imbalanced pro- and anti- inflammatory responses often leading to immune dysfunction. These injuries often exhibit delayed healing, leading to fibrosis of injury sites and delayed healing of fractures depending on the intensity of the compounding traumas. Immune dysfunction is accompanied by a temporal shift in the innate and adaptive immune cells distribution, triggered by the overwhelming release of an arsenal of inflammatory mediators such as complements, cytokines and damage associated molecular patterns (DAMPs) from necrotic cells. Recent studies have implicated this dysregulated inflammation in the poor prognosis of polytraumatic injuries, however, interventions focusing on immunomodulating inflammatory cellular composition and activation, if administered incorrectly, can result in immune suppression and unintended outcomes. Immunomodulation therapy is promising but should be conducted with consideration for the spatial and temporal distribution of the immune cells during impaired healing. This review describes the current state of knowledge in the spatiotemporal distribution patterns of immune cells at various stages during musculoskeletal wound healing, with a focus on recent advances in the field of Osteoimmunology, a study of the interface between the immune and skeletal systems, in long bone fractures. The goals of this review are to (1) discuss wound and fracture healing processes of normal and delayed healing in skeletal muscles and long bones; (2) provide a balanced perspective on temporal distributions of immune cells and skeletal cells during healing; and (3) highlight recent therapeutic interventions used to improve fracture healing. This review is intended to promote an understanding of the importance of inflammation during normal and delayed wound and fracture healing. Knowledge gained will be instrumental in developing novel immunomodulatory approaches for impaired healing.
Ramesh Subbiah, Marissa Ruehle, Brett S. Klosterhoff, Angela Sp Lin, Marian H. Hettiaratchi, Nick J. Willett, Luiz E. Bertassoni, Andrés J. García, Robert E. Guldberg
Published: 1 January 2020
SSRN Electronic Journal; doi:10.2139/ssrn.3737321

The publisher has not yet granted permission to display this abstract.
Th. Karachalios,
Calcified Tissue International, Volume 66, pp 165-167; doi:10.1007/pl00013136

The publisher has not yet granted permission to display this abstract.
Daniel Wu, Pasquale Razzano,
Published: 16 January 2003
by Wiley
Journal of Cellular Biochemistry, Volume 88, pp 467-481; doi:10.1002/jcb.10332

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N. C. Keramaris, E. Tsiridis, N. Malliaropoulos, A. Kostakos, A. Topkas, S. Pnevmatikos, P. J. Papagellopoulos, G. Sapkas
Published: 20 January 2011
by BMJ
British Journal of Sports Medicine, Volume 45; doi:10.1136/bjsm.2010.081554.32

The publisher has not yet granted permission to display this abstract.
Michael S. Valerio, Naveena B. Janakiram, ,
Published: 1 October 2020
Injury, Volume 51, pp 2099-2109; doi:10.1016/j.injury.2020.06.023

The publisher has not yet granted permission to display this abstract.
V B Duthon, M Ozturk, S El-Achachi, J Menetrey
Published: 16 July 2014
Revue medicale suisse, Volume 10

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, Phonepasong Arounleut, Ethan Kellum, Matthew Cain, David Immel, Li-Fang Liang
Journal of Trauma: Injury, Infection & Critical Care, Volume 69, pp 579-583; doi:10.1097/ta.0b013e3181c451f4

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Christian Isaac, Adam Wright, Arvydas Usas, Hongshuai Li, Ying Tang, Xiaodong Mu, Nicholas Greco, Qing Dong, Nam Vo, James Kang, et al.
Published: 23 October 2012
by Wiley
Journal of Orthopaedic Research, Volume 31, pp 343-349; doi:10.1002/jor.22236

Abstract:
Duchenne muscular dystrophy (DMD) is a degenerative muscle disorder characterized by the lack of dystrophin expression at the sarcolemma of muscle fibers. In addition, DMD patients acquire osteopenia, fragility fractures, and scoliosis indicating that a deficiency in skeletal homeostasis coexists but little is known about the effects of DMD on bone and other connective tissues within the musculoskeletal system. Recent evidence has emerged implicating adult stem cell dysfunction in DMD myopathogenesis. Given the common mesenchymal origin of muscle and bone, we sought to investigate bone and other musculoskeletal tissues in a DMD mouse model. Here, we report that dystrophin–utrophin double knockout (dko) mice exhibit a spectrum of degenerative changes, outside skeletal muscle, in bone, articular cartilage, and intervertebral discs, in addition to reduced lifespan, muscle degeneration, spinal deformity, and cardiomyopathy previously reported. We also report these mice to have a reduced capacity for bone healing and exhibit spontaneous heterotopic ossification in the hind limb muscles. Therefore, we propose the dko mouse as a model for premature musculoskeletal aging and posit that a similar phenomenon may occur in patients with DMD. © 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 31: 343–349, 2013
, Benjamin T. Corona, Jarrod A. Call
International Journal of Sports Medicine, Volume 41, pp 495-504; doi:10.1055/a-1128-7128

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Connie B. Scanga, Joseph J. Curci, Theresa Kyle, Rudy. Tassy, Allison Rusgo, Michelle Zappas, Ben Cocchiaro
Advanced Physiology and Pathophysiology; doi:10.1891/9780826177087.0016

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Medical Imaging in Clinical Trials pp 237-251; doi:10.1007/978-1-84882-710-3_11

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I Padmavathi
Archives of Anatomy and Physiology, Volume 4, pp 001-001; doi:10.17352/aap.000012

, Farah Tejpar
Masterful Care of the Aging Athlete pp 9-15; doi:10.1007/978-3-319-16223-2_2

The publisher has not yet granted permission to display this abstract.
, Marie K Reumann, , , Michael A Schuetz, , , Mohit Bhandari
Published: 1 September 2012
The Lancet, Volume 380, pp 1109-1119; doi:10.1016/s0140-6736(12)60991-x

The publisher has not yet granted permission to display this abstract.
Ke Ren, Xin Wei, Lingli Zhang,
Methods in Molecular Biology pp 389-412; doi:10.1007/978-1-4939-3121-7_20

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, Kunihiko Hayashi
Published: 23 January 2002
by Wiley
Bioelectromagnetics, Volume 23, pp 132-143; doi:10.1002/bem.106

The publisher has not yet granted permission to display this abstract.
Irwin M. Siegel
Published: 14 September 1984
JAMA, Volume 252, pp 1351-1352; doi:10.1001/jama.1984.03350100067038

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, Sinan Akay
Musculoskeletal Research and Basic Science pp 165-182; doi:10.1007/978-3-319-20777-3_10

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, J.P. Dillon, E.T. Condon, J.T. Street, J.H. Wang, A.J. McGuinness, H.P. Redmond
Published: 1 January 2006
by Wiley
Journal of Orthopaedic Research, Volume 25, pp 44-50; doi:10.1002/jor.20228

The publisher has not yet granted permission to display this abstract.
Tim Theologis
Musculoskeletal injuries in children; doi:10.1093/med/9780199550647.003.014001

The publisher has not yet granted permission to display this abstract.
J. Park, G. Yan, K.-C. Kwon, M. Liu, P.A. Gonnella, ,
Published: 1 March 2020
Biomaterials, Volume 233, pp 119591-119591; doi:10.1016/j.biomaterials.2019.119591

Abstract:
Human insulin-like growth factor-1 (IGF-1) plays important roles in development and regeneration of skeletal muscles and bones but requires daily injections or surgical implantation. Current clinical IGF-1 lacks e-peptide and is glycosylated, reducing functional efficacy. In this study, codon-optimized Pro-IGF-1 with e-peptide (fused to GM1 receptor binding protein CTB or cell penetrating peptide PTD) was expressed in lettuce chloroplasts to facilitate oral delivery. Pro-IGF-1 was expressed at high levels in the absence of the antibiotic resistance gene in lettuce chloroplasts and was maintained in subsequent generations. In lyophilized plant cells, Pro-IGF-1 maintained folding, assembly, stability and functionality up to 31 months, when stored at ambient temperature. CTB-Pro-IGF-1 stimulated proliferation of human oral keratinocytes, gingiva-derived mesenchymal stromal cells and mouse osteoblasts in a dose-dependent manner and promoted osteoblast differentiation through upregulation of ALP, OSX and RUNX2 genes. Mice orally gavaged with the lyophilized plant cells significantly increased IGF-1 levels in sera, skeletal muscles and was stable for several hours. When bioencapsulated CTB-Pro-IGF-1 was gavaged to femoral fractured diabetic mice, bone regeneration was significantly promoted with increase in bone volume, density and area. This novel delivery system should increase affordability and patient compliance, especially for treatment of musculoskeletal diseases.
, Daniele Vanni, Andrea Pantalone, Vincenzo Salini
Muscle Ligaments and Tendons Journal, Volume 3, pp 63-9; doi:10.11138/mltj/2013.3.2.063

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Dana C. Covey, R. Barry Lurate, Craig T. Hatton
Journal of Orthopaedic Trauma, Volume 14, pp 278-286; doi:10.1097/00005131-200005000-00010

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Tao Ji, , Rongli Yang, Xiaodong Tang, Dasen Li, Yi Yang
Zhongguo xiu fu chong jian wai ke za zhi = Zhongguo xiufu chongjian waike zazhi = Chinese journal of reparative and reconstructive surgery, Volume 31, pp 1161-1167; doi:10.7507/1002-1892.201705005

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