Background: Skeletal muscle fiber formation requires myoblast cell-cell membrane contact and fusion. Results: A versican-rich pericellular matrix surrounding myoblasts is proteolytically cleared by ADAMTS versicanases facilitating myoblast contact and fusion. Conclusion: Versican processing by ADAMTS versicanases contribute to muscle fiber formation. Significance: Targeting versican remodeling could enhance the regenerative capacity of muscle by improving muscle fiber fusion during regeneration.

BackgroundThe A Disintegrin-like and Metalloproteinase domain with Thrombospondin-1 motifs (ADAMTS) enzymes comprise 19 mammalian zinc-dependent metalloproteinases (metzincins) with homologues in a wide range of invertebrates. ADAMTS enzymes have a broad range of functions in development and diseases due to their extracellular matrix remodelling activity. Here, we report a detailed characterisation of their evolutionary conservation across vertebrates.ResultsUsing bioinformatics complemented with de novo sequencing, gene sequences for ADAMTS enzymes were obtained from a variety of organisms. Detailed evolutionary analyses revealed a high level of conservation across vertebrates with evidence of ADAMTS gene expansion during two rounds of whole genome duplication (WGD) in vertebrates, while tandem duplication events and gene loss were also apparent. However, the additional round of teleost-specific WGD did not have a significant effect on ADAMTS gene family members suggesting their conserved roles have remained constant in teleost fish. Quantitative reverse-transcriptase polymerase chain reaction analysis revealed dynamic expression of adamts genes throughout zebrafish embryonic development reflecting the key conserved roles they play in vertebrate embryogenesis. Notably, several adamts mRNAs were maternally expressed with a dramatic increase in mRNA levels coinciding with zygotic expression and organogenesis. Broad adamts mRNA expression was also demonstrated in several adult organs indicating potential roles in adult homeostasis.ConclusionsOur data highlight the evolution of the ADAMTS gene family through duplication processes across metazoans supplemented by a burst of amplification through vertebrate WGD events. It also strongly posits the zebrafish as a potential model species to further elucidate the function of ADAMTS enzymes during vertebrate development.Electronic supplementary materialThe online version of this article (doi:10.1186/s12862-015-0281-9) contains supplementary material, which is available to authorized users.

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Duchenne muscular dystrophy (DMD) is a lethal muscle wasting disorder caused by mutations in the DMD gene that lead to the absence or severe reduction of dystrophin protein in muscle. The mdx mouse, also dystrophin deficient, is the model most widely used to study the pathology and test potential therapies, but the phenotype is milder than human DMD. This limits the magnitude and range of histological damage parameters and molecular changes that can be measured in pre-clinical drug testing. We used three weeks of voluntary wheel running to exacerbate the mdx phenotype. In mdx mice voluntary exercise increased the amount of damaged necrotic tissue and macrophage infiltration. Global gene expression profiling revealed that exercise induced additional and larger gene expression changes in mdx mice and the pathways most impacted by exercise were all related to immune function or cell-extracellular matrix (ECM) interactions. When we compared the matrisome and inflammation genes that were dysregulated in mdx with those commonly differentially expressed in DMD, we found the exercised mdx molecular signature more closely resembled that of DMD. These gene expression changes in the exercised mdx model thus provide more scope to assess the effects of pre-clinical treatments. Our gene profiling comparisons also highlighted upregulation of extracellular matrix proteins involved in innate immunity pathways, proteases that can release them, and downstream receptors and signalling molecules in exercised mdx and DMD, suggesting that the ECM could be a major source of pro-inflammatory molecules that trigger and maintain the immune response in dystrophic muscle.

Background:The role endogenously synthesized hyaluronan plays in myogenesis is not yet known. Results: Hyaluronan synthase genes were expressed during skeletal muscle growth and regeneration; inhibiting these synthases prevents myoblast differentiation and fusion. Conclusion: Endogenous hyaluronan synthesis is required for myogenic differentiation. Significance: The necessity for hyaluronan in myogenesis has implications when considering promoting muscle growth or regeneration.

Objective: To investigate the changes in mental health and activities of children with chronic health conditions (CHC) during the pandemic. Additionally, to gather information from parents about healthcare experiences, family stressors and mental health during the COVID-19 pandemic. Design: A prospective longitudinal single site cohort study Setting: Royal Childrens Hospital, Melbourne, Australia Participants: 151 parents of children aged 1.5-17 years (M = 9.8 years, 58.3% male) with a CHC (colorectal disorder, cleft palate and neurofibromatosis type 1) completed the survey. Main outcome measures: An adapted version of the COVID-19 Wellbeing and Mental Health Survey for Children and Adolescents (Parent/Caregiver version) (CRISIS) was utilised. The CRISIS tool collects data on child activities and mental health and parent mental health prior to, and during, the COVID-19 pandemic. Healthcare experiences families was also examined. Parents completed the Kessler 10. Results: Compared to pre-COVID lockdown, parents reported their children were experiencing higher rates of loneliness, irritability, worry and anxiety. Parents reported that the restrictions in face-to-face contact with family and friends had been stressful for 80.0% of children. The activities of the children changed considerably during the COVID-19 pandemic with screen time increasing by 40%. Thirty percent of parents reported significant distress of their own. Parents felt telehealth were of poorer quality than face-to-face appointments. Conclusions: Children with CHC experienced a significant increase in mental health symptoms during lockdown for the COVID-19 pandemic. Our findings highlight the increased need for clinical monitoring for children with CHC during periods of community stress and restrictions.