Development and Regeneration of Muscle, Tendon, and Myotendinous Junctions in Striated Skeletal Muscle.

Masahito Yamamoto,Wei-Jen Chang,Takeshi Takayama,Shuichiro Taniguchi,Takahiro Takagi,Genji Watanabe,Shinichi Abe,Sayo Sekiya,Katsuhiko Hayashi,Koji Sakiyama,Satoshi Ishizuka,Yudai Ogawa,Yutaro Yamamoto,Yuki Sugiyama,Kei Kitamura

doi:10.3390/ijms23063006

Abstract

Owing to a rapid increase in aging population in recent years, the deterioration of motor function in older adults has become an important social problem, and several studies have aimed to investigate the mechanisms underlying muscle function decline. Furthermore, structural maintenance of the muscle–tendon–bone complexes in the muscle attachment sites is important for motor function, particularly for joints; however, the development and regeneration of these complexes have not been studied thoroughly and require further elucidation. Recent studies have provided insights into the roles of mesenchymal progenitors in the development and regeneration of muscles and myotendinous junctions. In particular, studies on muscles and myotendinous junctions have—through the use of the recently developed scRNA-seq—reported the presence of syncytia, thereby suggesting that fibroblasts may be transformed into myoblasts in a BMP-dependent manner. In addition, the high mobility group box 1—a DNA-binding protein found in nuclei—is reportedly involved in muscle regeneration. Furthermore, studies have identified several factors required for the formation of locomotor apparatuses, e.g., tenomodulin (Tnmd) and mohawk (Mkx), which are essential for tendon maturation.

Highlights

Skeletal muscle fibers are multinucleated myocytes that are formed after several stages; one such stage is myoblast fusion, which occurs as the body grows
Cell lineage analyses focusing on Scleraxis (CSX), a widely known tendon marker during development and tendon formation, and protein odd-skipped-related 1 (OSR1), a key regulator of muscle connective tissue differentiation, identified Pax7-positive cells originating from cell lineage analyses focusing on Scleraxis (CSX) and OSR1 lineages, respectively, at the muscle ends
They conducted an experiment in which a retrovirus was used to overexpress BMP4 or the bone morphogenetic protein (BMP) antagonist NOGGIN. They found that BMP overexpression induced the transformation of fibroblasts into myoblasts, whereas BMP suppression induced transformation into fibroblasts. These findings suggest the possibility that fibroblasts transform into myoblasts in a BMP-dependent manner in the process of limb formation

Summary

Introduction

Skeletal muscle fibers are multinucleated myocytes that are formed after several stages; one such stage is myoblast fusion, which occurs as the body grows. Sci. 2022, 23, 3006 muscle fiber and fibrous connective tissue markers They focused on paired related homeobox 1 (Prrx1), a specific marker of LPM-derived cells, and crossed Prrx1–Cre mice and various fluorescent reporter transgenic mice to attempt cell lineage analysis of the LPM. Cell lineage analyses focusing on Scleraxis (CSX), a widely known tendon marker during development and tendon formation, and protein odd-skipped-related 1 (OSR1), a key regulator of muscle connective tissue differentiation, identified Pax7-positive cells originating from CSX and OSR1 lineages, respectively, at the muscle ends. These results have shown the presence of limb connective tissue-derived, non-somite-derived, myogenic cells at the muscle ends. These findings indicate that the normal development of the quantity and polarity of muscle fibers constituting the tongue greatly contributes to breastfeeding, swallowing, and mastication in the early stages of life

Tendon

Part 2

Tendon Regeneration in Myotendinous Junctions

Effects of Mechanical Load on the Growth of Muscle Attachment Sites

Conclusions