Poor muscle coverage delays fracture healing in rats

Utvåg, Stein Erik; Iversen, Knut; Grundnes, Oliver; Reikerås, Olav

doi:10.1080/00016470216315

Cited by 45 publications

(39 citation statements)

References 18 publications

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“…Indeed, our earlier study utilizing a myostatin propeptide revealed that systemic injections of a myostatin inhibitor can enhance bone healing as well as muscle regeneration . Evidence shows that extensive muscle tissue injury has a negative impact on early bone healing (Utvag et al 2002), whereas open fractures show improved healing when covered with an intact muscle flap (Gopal et al 2000). It has also been reported that fracture callus size is increased in regions where there is abundant muscle coverage (Landry et al 2000) and that the muscle bed adjacent to the fracture site may contribute chondroprogenitor cells to the fracture hematoma (Pritchard and Ruzicka 1950).…”

Section: Discussionmentioning

confidence: 99%

“…Skeletal muscle is known to have important effects on bone healing (Stein et al 2002;Hamrick, McNeil, et al 2010;Hamrick, 2011). For example, muscle flaps are often used to promote and accelerate fracture repair (Gopal et al 2000), and significant damage to muscle tissue following traumatic orthopaedic injury is believed to delay and retard the normal fracture healing process (Utvag et al 2002). Thus, while muscle is known to play a key role in fracture healing and myostatin plays an important role in muscle regeneration, the role of myostatin in regulating musculoskeletal injury repair remains poorly understood.…”

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confidence: 99%

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Immunolocalization of Myostatin (GDF-8) Following Musculoskeletal Injury and the Effects of Exogenous Myostatin on Muscle and Bone Healing

Elkasrawy

Immel

Wen

et al. 2011

J Histochem Cytochem.

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SummaryThe time course and cellular localization of myostatin expression following musculoskeletal injury are not well understood; therefore, the authors evaluated the temporal and spatial localization of myostatin during muscle and bone repair following deep penetrant injury in a mouse model. They then used hydrogel delivery of exogenous myostatin in the same injury model to determine the effects of myostatin exposure on muscle and bone healing. Results showed that a "pool" of intense myostatin staining was observed among injured skeletal muscle fibers 12-24 hr postsurgery and that myostatin was also expressed in the soft callus chondrocytes 4 days following osteotomy. Hydrogel delivery of 10 or 100 µg/ml recombinant myostatin decreased fracture callus cartilage area relative to total callus area in a dose-dependent manner by 41% and 80% (p<0.05), respectively, compared to vehicle treatment. Myostatin treatment also decreased fracture callus total bone volume by 30.6% and 38.8% (p<0.05), with the higher dose of recombinant myostatin yielding the greatest decrease in callus bone volume. Finally, exogenous myostatin treatment caused a significant dose-dependent increase in fibrous tissue formation in skeletal muscle. Together, these findings suggest that early pharmacological inhibition of myostatin is likely to improve the regenerative potential of both muscle and bone following deep penetrant musculoskeletal injury. (J Histochem Cytochem 60:22-30, 2012)

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Immunolocalization of Myostatin (GDF-8) Following Musculoskeletal Injury and the Effects of Exogenous Myostatin on Muscle and Bone Healing

Elkasrawy

Immel

Wen

et al. 2011

J Histochem Cytochem.

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“…The muscular supply of uncommitted mesenchymal cells, osteoprogenitor cells and bone growth factors, may be important components in fracture repair tissue, in addition to the periosteum and endosteum. Utvå g et al 11,12 found that mild soft tissue injuries and muscle tissue injuries had an effect on the strength of the bone, despite normal vascularity being interrupted in an early stage of fracture healing, unless the muscle had been sheared off. Open fractures are associated with muscle and soft tissue damage, leading to changes in mechanical factors as well as biological factors.…”

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confidence: 99%

“…The vasculature is known to be critical for hard callus formation, and reduced blood flow in the local region potentially resulting in delayed fracture healing or nonunion. [10][11][12] Previous studies have analyzed effects of some damages, such as muscles broken and degeneration, on muscle function [12][13][14]18,19 suggested that the integrity of muscle tissue surrounding fracture sites is necessary for fracture repair. However, the influence of muscular atrophy and low muscle function in fracture healing is remaining unknown.…”

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confidence: 99%

Short‐term muscle atrophy caused by botulinum toxin‐A local injection impairs fracture healing in the rat femur

Hao

Wang

et al. 2011

Journal Orthopaedic Research

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Damaged bone is sensitive to mechanical stimulation throughout the remodeling phase of bone healing. Muscle damage and muscular atrophy associated with open fractures and subsequent fixation are not beneficial to maintaining optimum conditions for mechanical stability. The aim of this study was to investigate whether local muscle atrophy and dysfunction affect fracture healing in a rat femur fracture model. We combined the rat model of a short period atrophy of the quadriceps with femur fracture. Forty-fourmonth-old male Wistar rats were adopted for this study. Two units of botulinum toxin-A (BXTA) were administered locally into the right side of the quadriceps of each rat, while the same dose of saline was injected into the contralateral quadriceps. After BXTA had been fully absorbed by the quadriceps, osteotomy was performed in both femurs with intramedullary fixation. Gross observation and weighing of muscle tissue, X-ray analysis, callus histology, and bone biomechanical testing were performed at different time points up to 8 weeks post-surgery. Local injection of BXTA led to a significant decrease in the volume and weight of the quadriceps compared to the control side. At the eighth week, the left side femurs of the saline-injected quadriceps almost reached bony union, and fibrous calluses were completely calcified into woven bone. However, a gap was still visible in the BXTA-treated side on X-ray images. As showed by bone histology, there were no mature osseous calluses or woven bone on the BXTA-treated side, but a resorption pattern was evident. Biomechanical testing indicated that the femurs of the BXTA-treated side exhibited inferior mechanical properties compared with the control side. The inferior outcome following BXTA injection, compared with saline injection, in terms of callus resistance may be the consequence of unexpected load and mechanical unsteadiness caused by muscle atrophy and dysfunction. ß

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“…inhibits mechanically induced bone cell proliferation [20], and (2) neurectomized individuals exhibit muscular atrophy, which may impair osteogenesis [38,39]. Some inflammatory mediators present during fracture healing may regulate bone cells response to LIPUS so that there is a cumulate rather than noncumulative effect on fractured bone; this being the case, LIPUS could increase osteogenesis in fractured bone [2,15].…”

Section: Discussionmentioning

confidence: 99%

Low-intensity Ultrasound Increases FAK, ERK-1/2, and IRS-1 Expression of Intact Rat Bones in a Noncumulative Manner

Gusmão

Pauli

Saad

et al. 2010

Clinical Orthopaedics &Amp; Related Research

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Background Low-intensity pulsed ultrasound stimulation (LIPUS) reportedly increases osteogenesis in fracture models but fails in intact bone, suggesting LIPUS does not act on mechanotransduction and growth factor pathways of intact bone. Questions/Purposes We asked whether daily 20-minute LIPUS applied to intact tibias would act on bone proteins involved in mechanotransduction (focal adhesion kinase [FAK], and extracellular signal-regulated kinase-1/2 [ERK-1/2]), and growth factor signaling (insulin receptor substrate-1 [IRS-1]) pathways at 7, 14, and 21 days of treatment.Methods Immunoblotting was performed to detect FAK, ERK-1/2, and IRS-1 expression and activation from the stimulated intact tibias at 7, 14, and 21 days of daily 20-minute LIPUS. Results LIPUS increased FAK expression (at 7 days), ERK-1/2 (at 14 days), and IRS-1 (at 7 days), but expression decreased 7 days later, indicating a noncumulative effect of LIPUS. As only FAK expression was detected at 21 days, these observations suggest LIPUS influences nuclear reactions that may be modulated by a major cellular mechanism preferentially inhibiting IRS-1 expression and not FAK expression. Increased ERK-1/2 expression at 14 days suggests the differing mechanisms for promoting ERK-1/2, FAK, and IRS-1 syntheses. IRS-1 expression behaved similarly to FAK expression; therefore, LIPUS may modulate growth factor pathways. LIPUS increased sustained FAK and ERK-1/2 activation, but not IRS-1, suggesting sustained ERK-1/2 activation is not the result of mechanically induced growth factor activation. Conclusions LIPUS acts on mechanotransduction and growth factor pathways in intact bone in a noncumulative manner. Clinical relevance These data suggest LIPUS applied to intact bone acts on proteins involved in osteogenesis.

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Poor muscle coverage delays fracture healing in rats

Cited by 45 publications

References 18 publications

Immunolocalization of Myostatin (GDF-8) Following Musculoskeletal Injury and the Effects of Exogenous Myostatin on Muscle and Bone Healing

Immunolocalization of Myostatin (GDF-8) Following Musculoskeletal Injury and the Effects of Exogenous Myostatin on Muscle and Bone Healing

Short‐term muscle atrophy caused by botulinum toxin‐A local injection impairs fracture healing in the rat femur

Low-intensity Ultrasound Increases FAK, ERK-1/2, and IRS-1 Expression of Intact Rat Bones in a Noncumulative Manner

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