Comparative Analysis of the Extracellular Matrix Proteome across the Myotendinous Junction

Jacobson, Kathryn R.; Lipp, Sarah N.; Acuna, Andrea; Leng, Yue; Bu, Ye; Calve, Sarah

doi:10.1021/acs.jproteome.0c00248

Cited by 48 publications

(65 citation statements)

References 101 publications

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“…(Fig.S3B) In other words, these genes may work as candidates for important drivers of the main process in firboNPCs. These genes have been associated with matrix remodeling (Col14A1, col12a1, CHAD, CRTAC1, TNC, Lamb1) 39 , antioxidation (FTH1) 40 and inflammation (S100a8) 41 .…”

Section: Resultsmentioning

confidence: 99%

Single-cell transcriptome profiling reveals multicellular ecosystem of nucleus pulposus during degeneration progression

Yang

et al. 2021

Preprint

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Degeneration of the nucleus pulposus (NP) is a major contributor to intervertebral disc degeneration (IVDD) and low back pain. However, the underlying molecular complexity and cellular heterogeneity remain poorly understood. Here, we first reported a comprehensive single-cell resolution transcriptional landscape of human NP. Six novel human nucleus pulposus cell (NPCs) populations were identified by distinct molecular signatures. The potential functional differences among NPC subpopulations were analyzed at the single-cell level. Predictive genes, transcriptional factors, and signal pathways with respect to degeneration grades were analyzed. We reported that fibroNPCs, one of our identified subpopulations, might be a population for NP regeneration. CD90+NPCs were observed to be progenitor cells in degenerative NP tissues. NP-infiltrating immune cells comprise a previously unrecognized diversity of cell types, including granulocytic myeloid-derived suppressor cells (G-MDSCs). We uncovered CD11b, OLR1, and CD24 as surface markers of NP-derived G-MDSCs. The G-MDSCs were also found to be enriched in mildly degenerated (grade I and II) NP tissues compared to severely degenerated (grade III and IV) NP tissues. Their immunosuppressive function and protective effects for NPCs were revealed . Collectively, this study revealed the NPC type complexity and phenotypic characteristics in NP, providing new insights and clues for IVDD treatment.

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Section: Resultsmentioning

confidence: 99%

Single-cell transcriptome profiling reveals multicellular ecosystem of nucleus pulposus during degeneration progression

Yang

et al. 2021

Preprint

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“…Understanding that sarcoplasmatic invaginations and SCL are composed of collagen fibers, we suggest SCL changes as precursors in the ultrastructural remodeling of MTJ. Jacobson et al (2020) described several collagen types in MTJ, more specifically, collagen XXII, which plays an essential role in the structural integrity and stabilization of the region.…”

Section: Discussionmentioning

confidence: 99%

Myotendinous Junction Components of Different Skeletal Muscles Present Morphological Changes in Obese Rats

et al. 2021

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“…Protein analysis of the ECM of muscle-tendon units revealed that there are several proteins, specifically type V α3 collagen, and type XXII collagen, that occur primarily at the junction. 10,11 Research into this specific protein synthesis could inform strategies for development of native-like muscle-tendon interfaces, increasing the function and efficacy of engineered muscle-tendon units. Future studies should include analysis of additional MTJ specific proteins like type XXII collagen, over longer time periods, along with cell signaling pathways leading to increased focal adhesion expression.…”

Section: Discussionmentioning

confidence: 99%

“…8,9 In studies of proteomic analysis of muscle-tendon units, type XXII collagen was isolated in the myotendinous region and is thought to interact with α7β1 integrins. 10,11 While there is some understanding of the cellular response to various disorders in muscle and tendon tissue individually, there is less understanding of how disorders in a single tissue may further inhibit reparative processes and decrease function of the muscle-tendon unit.…”

Section: Introductionmentioning

confidence: 99%

Extracellular Matrix Hydrogels Promote Expression of Muscle-Tendon Junction Proteins

Gaffney

Davis

Mora-Navarro

et al. 2021

Preprint

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Muscle and tendon injuries are prevalent and range from minor sprains and strains to traumatic, debilitating injuries. However, the interactions between these tissues during injury and recovery remain unclear. Three-dimensional tissue models that incorporate both tissues and a physiologically relevant junction between muscle and tendon may aide in understanding how the two tissues interact. Here, we use tissue specific extracellular matrix (ECM) derived from muscle and tendon to determine how cells of each tissue interact with the microenvironment of the opposite tissue resulting in junction specific features. ECM materials were derived from the achilles tendon and gastrocnemius muscle, decellularized, and processed to form tissue specific pre-hydrogel digests. C2C12 myoblasts and tendon fibroblasts were cultured in tissue-specific ECM conditioned media or encapsulated in tissue-specific ECM hydrogels to determine cell-matrix interactions and the effects on a muscle-tendon junction marker, paxillin. ECM conditioned media had only a minor effect on upregulation of paxillin in cells cultured in monolayer. However, cells cultured within ECM hydrogels had 50-70% higher paxillin expression than cells cultured in type I collagen hydrogels. Contraction of the ECM hydrogels varied by the type of ECM used. Subsequent experiments with varying density of type I collagen (and thus contraction) showed no correlation between paxillin expression and the amount of gel contraction, suggesting that a constituent of the ECM was the driver of paxillin expression in the ECM hydrogels. Using tissue specific ECM allowed for the de-construction of the cell-matrix interactions similar to muscle-tendon junctions to study the expression of MTJ specific proteins.Impact StatementThe muscle-tendon junction is an important feature of muscle-tendon units; however, despite cross-talk between the two tissue types, it is overlooked in current research. Deconstructing the cell-matrix interactions will allow the opportunity to study significant junction specific features and markers that should be included in tissue models of the muscle-tendon unit, while gaining a deeper understanding of the natural junction. This research aims to inform future methods to engineer a more relevant multi-tissue platform to study the muscle-tendon unit.

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Comparative Analysis of the Extracellular Matrix Proteome across the Myotendinous Junction

Cited by 48 publications

References 101 publications

Single-cell transcriptome profiling reveals multicellular ecosystem of nucleus pulposus during degeneration progression

Single-cell transcriptome profiling reveals multicellular ecosystem of nucleus pulposus during degeneration progression

Myotendinous Junction Components of Different Skeletal Muscles Present Morphological Changes in Obese Rats

Extracellular Matrix Hydrogels Promote Expression of Muscle-Tendon Junction Proteins

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