Implication of anti-inflammatory macrophages in regenerative moto-neuritogenesis: Promotion of myoblast migration and neural chemorepellent semaphorin 3A expression in injured muscle

Sakaguchi, Shohei; Shono, Jun ichi; Suzuki, Takahiro; Sawano, Shoko; Anderson, Judy E.; Q., Mai Khoi; Ohtsubo, Hideaki; Mizunoya, Wataru; Sato, Yusuke; Nakamura, Mako; Furuse, Mitsuhiro; Yamada, Koji; Ikeuchi, Yoshihide; Tatsumi, Ryuichi

doi:10.1016/j.biocel.2014.05.032

Cited by 41 publications

(39 citation statements)

References 92 publications

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“…A, B). These emerging results directly support our finding that myoblast‐secreted Sema3A ligand plays an essential role in slow‐fiber “commitment” during myotube formation period, as characterized by histological observations that revealed many mono‐nucleated cells and thin centrally‐nucleated myotubes in remnant areas of disrupted mature fibers .…”

Section: Resultssupporting

confidence: 88%

“…F). Overall, these in vitro results demonstrate that the Sema3A ligand has an impact on the formation of slow‐MyHC‐positive myotubes during the myotube formation period that corresponds to days 3–7 during in vivo regeneration from muscle injury by crush or CTX injection (see ).…”

Section: Resultsmentioning

confidence: 69%

“…received a unilateral CTX injection into lower hind‐limb muscles (tibialis anterior muscle and medial and lateral heads of gastrocnemius muscle on the right side). Gastrocnemius muscles were then evaluated for phenotypes of regenerative myogenesis at 0‐day (before injury), 5‐days (myotube‐formation time‐point), and 28‐days post‐injury (when muscle regeneration is typically complete, as shown previously ) (Fig. B, C, H, I, n = 3 at each time‐point).…”

Section: Resultsmentioning

confidence: 96%

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Slow-Myofiber Commitment by Semaphorin 3A Secreted from Myogenic Stem Cells

Tatsumi¹,

Suzuki

Q.³

et al. 2017

Stem Cells

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Recently, we found that resident myogenic stem satellite cells upregulate a multi-functional secreted protein, semaphorin 3A (Sema3A), exclusively at the early-differentiation phase in response to muscle injury; however, its physiological significance is still unknown. Here we show that Sema3A impacts slow-twitch fiber generation through a signaling pathway, cell-membrane receptor (neuropilin2-plexinA3) → myogenin-myocyte enhancer factor 2D → slow myosin heavy chain. This novel axis was found by small interfering RNA-transfection experiments in myoblast cultures, which also revealed an additional element that Sema3A-neuropilin1/plexinA1, A2 may enhance slow-fiber formation by activating signals that inhibit fast-myosin expression. Importantly, satellite cell-specific Sema3A conditional-knockout adult mice (Pax7CreER -Sema3A ° activated by tamoxifen-i.p. injection) provided direct in vivo evidence for the Sema3A-driven program, by showing that slow-fiber generation and muscle endurance were diminished after repair from cardiotoxin-injury of gastrocnemius muscle. Overall, the findings highlight an active role for satellite cell-secreted Sema3A ligand as a key "commitment factor" for the slow-fiber population during muscle regeneration. Results extend our understanding of the myogenic stem-cell strategy that regulates fiber-type differentiation and is responsible for skeletal muscle contractility, energy metabolism, fatigue resistance, and its susceptibility to aging and disease. Stem Cells 2017;35:1815-1834.

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Section: Resultssupporting

confidence: 88%

Section: Resultsmentioning

confidence: 69%

Section: Resultsmentioning

confidence: 96%

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Slow-Myofiber Commitment by Semaphorin 3A Secreted from Myogenic Stem Cells

Tatsumi¹,

Suzuki

Q.³

et al. 2017

Stem Cells

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“…2013; Sakaguchi et al. 2014; Sawano et al. 2014) with myoblasts (via activation of the SDC2, 4 receptor and induction of Sema3A secretion) and a motoneuron terminal (Sema3A target).…”

Section: Resultsmentioning

confidence: 99%

Transmembrane proteoglycans syndecan-2, 4, receptor candidates for the impact of HGF and FGF2 on semaphorin 3A expression in early-differentiated myoblasts

Shimizu

Suzuki

et al. 2015

Physiol Rep

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Regenerative mechanisms that regulate intramuscular motor innervation are thought to reside in the spatiotemporal expression of axon-guidance molecules. Our previous studies proposed an unexplored role of resident myogenic stem cell (satellite cell)-derived myoblasts as a key presenter of a secreted neural chemorepellent semaphorin 3A (Sema3A); hepatocyte growth factor (HGF) and basic fibroblast growth factor (FGF2) triggered its expression exclusively at the early differentiation phase. In order to advance this concept, the present study described that transmembrane heparan/chondroitin sulfate proteoglycans syndecan-2, 4 may be the plausible receptor candidates for HGF and FGF2 to signal Sema3A expression. Results showed that mRNA expression of syndecan-2, 4 was abundant (two magnitudes higher than syndecan-1, 3) in early-differentiated myoblasts and their in vitro knockdown diminished the HGF/FGF2-induced expression of Sema3A down to a baseline level. Pretreatment with heparitinase and chondroitinase ABC decreased the HGF and FGF2 responses, respectively, in non–knockdown cultures, supporting a possible model that HGF and FGF2 may bind to heparan and chondroitin sulfate chains of syndecan-2, 4 to signal Sema3A expression. The findings, therefore, extend our understanding that HGF/FGF2-syndecan-2, 4 association may stimulate a burst of Sema3A secretion by myoblasts recruited to the site of muscle injury; this would ensure a coordinated delay in the attachment of motoneuron terminals onto fibers early in muscle regeneration, and thus synchronize the recovery of muscle fiber integrity and the early resolution of inflammation after injury with reinnervation toward functional recovery.

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“…Muscle repair also features two heparin-binding growth factors, HGF and FGF, which are sequestered and presented at the ECM to facilitate regeneration. HGF has recently been shown to be derived from paracrine sources such as activated M2 macrophages but can also be secreted by proliferating satellite cells (Sakaguchi et al, 2014). HGF plays a fundamental role during the early stages of muscle regeneration by stimulating the migration and activation of satellite cells.…”

Section: Muscle Repair and Ossificationmentioning

confidence: 99%

Defining the Balance between Regeneration and Pathological Ossification in Skeletal Muscle Following Traumatic Injury

et al. 2017

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Heterotopic ossification (HO) is characterized by the formation of bone at atypical sites. This type of ectopic bone formation is most prominent in skeletal muscle, most frequently resulting as a consequence of physical trauma and associated with aberrant tissue regeneration. The condition is debilitating, reducing a patient's range of motion and potentially causing severe pathologies resulting from nerve and vascular compression. Despite efforts to understand the pathological processes governing HO, there remains a lack of consensus regarding the micro-environmental conditions conducive to its formation, and attempting to define the balance between muscle regeneration and pathological ossification remains complex. The development of HO is thought to be related to a complex interplay between factors released both locally and systemically in response to trauma. It develops as skeletal muscle undergoes significant repair and regeneration, and is likely to result from the misdirected differentiation of endogenous or systemically derived progenitors in response to biochemical and/or environmental cues. The process can be sequentially delineated by the presence of inflammation, tissue breakdown, adipogenesis, hypoxia, neo-vasculogenesis, chondrogenesis and ossification. However, exactly how each of these stages contributes to the formation of HO is at present not well understood. Our previous review examined the cellular contribution to HO. Therefore, the principal aim of this review will be to comprehensively outline changes in the local tissue micro-environment following trauma, and identify how these changes can alter the balance between skeletal muscle regeneration and ectopic ossification. An understanding of the mechanisms governing this condition is required for the development and advancement of HO prophylaxis and treatment, and may even hold the key to unlocking novel methods for engineering hard tissues.

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Implication of anti-inflammatory macrophages in regenerative moto-neuritogenesis: Promotion of myoblast migration and neural chemorepellent semaphorin 3A expression in injured muscle

Cited by 41 publications

References 92 publications

Slow-Myofiber Commitment by Semaphorin 3A Secreted from Myogenic Stem Cells

Slow-Myofiber Commitment by Semaphorin 3A Secreted from Myogenic Stem Cells

Transmembrane proteoglycans syndecan-2, 4, receptor candidates for the impact of HGF and FGF2 on semaphorin 3A expression in early-differentiated myoblasts

Defining the Balance between Regeneration and Pathological Ossification in Skeletal Muscle Following Traumatic Injury

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