Wrist Arthrodesis Following Ulnar Bar Excision in Fibrodysplasia Ossificans Progressiva

Fibrodysplasia ossificans progressiva is a rare disorder characterized by the progressive development of heterotopic bone in the connective tissues of skeletal muscle, ligaments and tendons. Surgical trauma is one of the most potent stimuli for ossification and surgical treatment is generally considered to be contraindicated in this condition. We report a good functional result in a patient with severe hand disability secondary to an ulna-carpal bar in fibrodysplasia ossificans progressiva.

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The unique activity of bone morphogenetic proteins in bone: a critical role of the Smad signaling pathway

Biological Chemistry ◽

10.1515/hsz-2012-0310 ◽

2013 ◽

Vol 394 (6) ◽

pp. 703-714 ◽

Cited By ~ 40

Author(s):

Takenobu Katagiri ◽

Sho Tsukamoto

Keyword(s):

Skeletal Muscle ◽

Transcription Factors ◽

Bone Formation ◽

Bone Morphogenetic Proteins ◽

Fibrodysplasia Ossificans Progressiva ◽

Type I ◽

Heterotopic Bone ◽

Heterotopic Bone Formation ◽

Smad Signaling ◽

Smad Signaling Pathway

Abstract Bone morphogenetic proteins (BMPs) are multifunctional cytokines that belong to the transforming growth factor-β family. BMPs were originally identified based on their unique activity, inducing heterotopic bone formation in skeletal muscle. This unique BMP activity is transduced by specific type I and type II transmembrane kinase receptors. Among the downstream pathways activated by these receptors, the Smad1/5/8 transcription factors appear to play critical roles in BMP activity. Smad1/5/8 transcription factors are phosphorylated at the C-terminal SVS motif by BMP type I receptors and then induce the transcription of early BMP-responsive genes by binding to conserved sequences in their enhancer regions. The linker regions of Smad1/5/8 contain multiple kinase phosphorylation sites, and phosphorylation and dephosphorylation of these sites regulate the transcriptional activity of Smad proteins. Gain-of-function mutations in one BMP type I receptor have been identified in patients with fibrodysplasia ossificans progressiva, a rare genetic disorder that is characterized by progressive heterotopic bone formation in the skeletal muscle. The mutant receptors activate the Smad signaling pathway even in the absence of BMPs, therefore novel inhibitors for the BMP receptor – Smad axis are being developed to prevent heterotopic bone formation in fibrodysplasia ossificans progressiva. Taken together, the data in the literature show that the BMP type I receptor – Smad signaling axis is the critical pathway for the unique activity of BMPs and is a potential therapeutic target for pathological conditions caused by inappropriate BMP activity.

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Dynamics of skeletal muscle-resident stem cells during myogenesis in fibrodysplasia ossificans progressiva

npj Regenerative Medicine ◽

10.1038/s41536-021-00201-8 ◽

2022 ◽

Vol 7 (1) ◽

Author(s):

Alexandra Stanley ◽

Elisia D. Tichy ◽

Jacob Kocan ◽

Douglas W. Roberts ◽

Eileen M. Shore ◽

...

Keyword(s):

Skeletal Muscle ◽

Stem Cells ◽

Skeletal Muscles ◽

Skeletal Muscle Regeneration ◽

Fibrodysplasia Ossificans Progressiva ◽

Type I ◽

Heterotopic Bone ◽

Differentiation Potential ◽

Resident Stem Cells

AbstractFibrodysplasia ossificans progressiva (FOP) is a rare genetic disease in which extraskeletal (heterotopic) bone forms within tissues such as skeletal muscles, often in response to injury. Mutations in the BMP type I receptor ACVR1/ALK2 cause FOP by increasing BMP pathway signaling. In contrast to the growing understanding of the inappropriate formation of bone tissue within the muscle in FOP, much is still unknown about the regenerative capacity of adult diseased muscles. Utilizing an inducible ACVR1R206H knock-in mouse, we found that injured Acvr1R206H/+ skeletal muscle tissue regenerates poorly. We demonstrated that while two resident stem cell populations, muscle stem cells (MuSCs) and fibro/adipogenic progenitors (FAPs), have similar proliferation rates after injury, the differentiation potential of mutant MuSCs is compromised. Although MuSC-specific deletion of the ACVR1R206H mutation does not alter the regenerative potential of skeletal muscles in vivo, Acvr1R206H/+ MuSCs form underdeveloped fibers that fail to fuse in vitro. We further determined that FAPs from Acvr1R206H/+ mice repress the MuSC-mediated formation of Acvr1R206H/+ myotubes in vitro. These results identify a previously unrecognized role for ACVR1R206H in myogenesis in FOP, via improper interaction of tissue-resident stem cells during skeletal muscle regeneration.

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Treadmill running causes significant fiber damage in skeletal muscle of KATP channel-deficient mice

Physiological Genomics ◽

10.1152/physiolgenomics.00064.2005 ◽

2005 ◽

Vol 22 (2) ◽

pp. 204-212 ◽

Cited By ~ 31

Author(s):

M. Thabet ◽

T. Miki ◽

S. Seino ◽

J.-M. Renaud

Keyword(s):

Skeletal Muscle ◽

Muscle Fibers ◽

Treadmill Running ◽

Wild Type ◽

Connective Tissues ◽

Fiber Damage ◽

Hindlimb Muscles ◽

Skeletal Muscle Fibers ◽

And Function ◽

Deficient Mice

Although it has been suggested that the ATP-sensitive K+ (KATP) channel protects muscle against function impairment, most studies have so far given little evidence for significant perturbation in the integrity and function of skeletal muscle fibers from inactive mice that lack KATP channel activity in their cell membrane. The objective was, therefore, to test the hypothesis that KATP channel-deficient skeletal muscle fibers become damaged when mice are subjected to stress. Wild-type and KATP channel-deficient mice (Kir6.2−/− mice) were subjected to 4–5 wk of treadmill running at either 20 m/min with 0° inclination or at 24 m/min with 20° uphill inclination. Muscles of all wild-type mice and of nonexercised Kir6.2−/− mice had very few fibers with internal nuclei. After 4–5 wk of treadmill running, there was little evidence for connective tissues and mononucleated cells in Kir6.2−/− hindlimb muscles, whereas the number of fibers with internal nuclei, which appear when damaged fibers are regenerated by satellite cells, was significantly higher in Kir6.2−/− than wild-type mice. Between 5% and 25% of the total number of fibers in Kir6.2−/− extensor digitum longus, plantaris, and tibialis muscles had internal nuclei, and most of such fibers were type IIB fibers. Contrary to hindlimb muscles, diaphragms of Kir6.2−/− mice that had run at 24 m/min had few fibers with internal nuclei, but mild to severe fiber damage was observed. In conclusion, the study provides for the first time evidence 1) that the KATP channels of skeletal muscle are essential to prevent fiber damage, and thus muscle dysfunction; and 2) that the extent of fiber damage is greater and the capacity of fiber regeneration is less in Kir6.2−/− diaphragm muscles compared with hindlimb muscles.

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Age and tissue specific differences in the development of acute insulin resistance following injury

Journal of Endocrinology ◽

10.1677/joe-09-0269 ◽

2009 ◽

Vol 203 (3) ◽

pp. 365-374 ◽

Cited By ~ 10

Author(s):

Lidong Zhai ◽

Joseph L Messina

Keyword(s):

Insulin Resistance ◽

Skeletal Muscle ◽

Insulin Signaling ◽

Intracellular Signaling ◽

Male Rats ◽

Hepatic Insulin Resistance ◽

Surgical Trauma ◽

Induce Insulin Resistance ◽

Old Rats ◽

Effect Of Age

Injuries, hemorrhage, sepsis, burn, and critical illnesses all induce insulin resistance, and insulin resistance is strongly associated with advancing age. However, the effect of age on injury induced insulin resistance is not well studied. We performed surgical trauma in male rats of three different ages (3-, 6-, and 10-weeks old). Rats were either hemorrhaged to a mean arterial pressure of 35–40 mmHg and subsequently maintained at that pressure for up to 90 min, or maintained without hemorrhage as controls. Results indicate that insulin-induced intracellular signaling was diminished in liver and skeletal muscle of 6- and 10-week old rats following trauma and hemorrhage. In even younger rats, immediately post-weaning (∼3 weeks of age), insulin signaling was lost in liver, but not in skeletal muscle. Glucocorticoids can play a role in the chronic development of insulin resistance. Our results demonstrate that corticosterone levels were increased in 6- and 10-week old animals following hemorrhage, but little change was measured in 3-week old animals. Blockade of glucocorticoid synthesis prevented the development of insulin resistance in skeletal muscle, but not in liver of 6- and 10-week old rats. Moreover, skeletal muscle glucocorticoid receptor levels increased dramatically between 3 and 6 weeks of age. These results indicate that trauma and hemorrhage-induced hepatic insulin resistance occurs at all ages tested. However, there is no development of insulin resistance following trauma and hemorrhage in skeletal muscle of post-weaning rats. In skeletal muscle of 6- and 10-week old rats, inhibition of glucocorticoid levels prevents the development of insulin resistance.

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Surgical trauma decreases glutathione synthetic capacity in human skeletal muscle tissue

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1998.275.2.e359 ◽

1998 ◽

Vol 275 (2) ◽

pp. E359-E365 ◽

Cited By ~ 12

Author(s):

Jia-Li Luo ◽

Folke Hammarqvist ◽

Kerstin Andersson ◽

Jan Wernerman

Keyword(s):

Skeletal Muscle ◽

Muscle Tissue ◽

Redox Status ◽

Skeletal Muscle Tissue ◽

Surgical Trauma ◽

Synthetase Activity ◽

Glutamylcysteine Synthetase ◽

Gsh Metabolism ◽

Synthetic Capacity ◽

Femoris Muscle

To gain insight into cellular metabolism underlying the glutathione (GSH) alterations induced by surgical trauma, we assessed postoperative skeletal muscle GSH metabolism and its redox status in 10 patients undergoing elective abdominal surgery. Muscle biopsy specimens were taken from the quadriceps femoris muscle before and at 24 and 72 h after surgery. GSH concentrations decreased by 40% at 24 h postoperatively compared with the paired preoperative values ( P < 0.001) and remained low at 72 h ( P < 0.01). The concentration of GSH disulfide (GSSG) did not significantly change throughout the study period, whereas the total GSH (as GSH equivalent) concentration decreased after surgery. Of the GSH constituent amino acids, the concentration of cysteine remained unchanged throughout the study period (from 28.2 ± 10.1 preoperatively to 29.4 ± 13.9 at 24 h postoperatively and to 28.3 ± 15.6 μmol/kg wet wt at 72 h postoperatively). Despite a reduction in glutamate concentration by 40% 24 h after surgery, no correlation was established between GSH and glutamate concentrations postoperatively. Activity of γ-glutamylcysteine synthetase did not change significantly after surgery, whereas GSH synthetase activity decreased postoperatively (from 66.4 ± 19.1 preoperatively to 41.0 ± 10.5 24 h postoperatively, P < 0.01, and to 46.0 ± 11.7 μU/mg protein 72 h postoperatively, P < 0.05). The decrease of GSH was correlated to the reduced GSH synthetase activity seen at 24 h postoperatively. These results indicate that the skeletal muscle GSH pool is diminished in patients after surgical trauma. The depletion of the GSH pool is associated with a decreased activity of GSH synthetase, indicating a decreased GSH synthetic capacity in skeletal muscle tissue.

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Distally Based Sural Flap in Children: Reliability Technique

European Journal of Medical and Health Sciences ◽

10.24018/ejmed.2021.3.5.1015 ◽

2021 ◽

Vol 3 (5) ◽

pp. 29-31

Author(s):

A. Benjelloun ◽

N. Belmoudden ◽

M. Habla ◽

M. Benkhaldoun ◽

A. Elharti ◽

...

Keyword(s):

Functional Result ◽

Vascular Complications ◽

Sural Flap ◽

Good Functional Result ◽

Distally Based ◽

The Aesthetic ◽

Distally Based Sural Flap

The distally based sural flap often poses the problem of venous suffering that can lead to necrosis. We present a reconstruction of a loss of substance of the ankle in a 6 years old child, using a distal pedicle sural flap, made reliable by a racket like flap method, which reduces the risk of vascular complications and led to good integration of the flap, with a good functional result. Nevertheless, the aesthetic sequelae remain significant.

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Glutathione in human skeletal muscle: effects of foodintake, surgical trauma and critical illness

Clinical Nutrition ◽

10.1016/s0261-5614(97)80242-7 ◽

1997 ◽

Vol 16 (3) ◽

pp. 141-143 ◽

Cited By ~ 1

Author(s):

J.-L. Luo ◽

F. Hammarovist ◽

K. Andersson ◽

J. Wernerman

Keyword(s):

Skeletal Muscle ◽

Critical Illness ◽

Human Skeletal Muscle ◽

Surgical Trauma

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Effect of carbohydrate feeding on insulin action in skeletal muscle after surgical trauma in the rat

Nutrition ◽

10.1016/s0899-9007(00)00587-6 ◽

2001 ◽

Vol 17 (4) ◽

pp. 332-336 ◽

Cited By ~ 7

Author(s):

Lisa Strömmer ◽

Bengt Isaksson ◽

Malin Wickbom ◽

Urban Arnelo ◽

Claes-Göran Östenson ◽

...

Keyword(s):

Skeletal Muscle ◽

Insulin Action ◽

Surgical Trauma ◽

Carbohydrate Feeding

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Impact of surgical trauma on human skeletal muscle protein synthesis

Clinical Science ◽

10.1042/cs20040192 ◽

2004 ◽

Vol 107 (6) ◽

pp. 601-607 ◽

Cited By ~ 6

Author(s):

Inga TJÄDER ◽

Pia ESSEN ◽

Peter J. GARLICK ◽

Margaret A. McMNURLAN ◽

Olav ROOYACKERS ◽

...

Keyword(s):

Skeletal Muscle ◽

Protein Synthesis ◽

Pilot Study ◽

Muscle Protein ◽

Muscle Protein Synthesis ◽

Major Surgery ◽

Synthesis Rate ◽

Protein Synthesis Rate ◽

Surgical Trauma ◽

Minor Surgery

Muscle protein catabolism is a considerable clinical problem following surgery. However, the impact of surgical trauma on muscle protein synthesis is not well characterized. In this pilot study, we therefore investigated whether the severity of surgical trauma is related to a decrease in muscle protein synthesis rate in humans. Metabolically healthy patients (n=28) were included in the study. Eight of the patients were day-care patients undergoing minor breast surgery (defined as minor surgery). The other 20 patients were subjected to major abdominal surgery and were therefore scheduled to stay overnight in the recovery room during the first postoperative night (defined as major surgery). Protein FSRs (fractional synthesis rates) in skeletal muscle were determined during a measurement period of 90 min before surgery and immediately after termination of surgery. FSR in skeletal muscle of the minor surgery patients was 1.72±0.25%/24 h before surgery and 1.67±0.29%/24 h after surgery (P=0.68). In the major surgery group, FSR was 1.62±0.30%/24 h before surgery and 1.57±0.40%/24 h (P=0.59) immediately following surgery. The observations made in this pilot study could not confirm a size-related decrease in muscle protein synthesis immediately following minor and major surgery. This finding is discussed in relation to confounders, postoperative course and to muscle protein degradation. The shortage of knowledge in this field is emphasized.

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