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The myotendinous junction (MTJ) is a weak link in the musculoskeletal system. Here, we isolated the tips of single myofibres from healthy human hamstring muscles for confocal microscopy (n=6) and RNAscope in situ hybridization (n=6) to gain insight into the profiles of cells and myonuclei in this region. A marked presence of mononuclear cells was observed coating the fibre tips, with a median of 29 (range 16-63) and 16 (9-23) cells per fibre for type I and II myofibres, respectively (p<0.05). The number and density of myonuclei gradually increased from the myofibre proper towards the tip (p<0.05), similarly for both fibre types, and a greater number of COL22A1-expressing nuclei was seen in type II vs type I myofibres (p<0.05). These divergent fibre type-specific characteristics of the MTJ reflect the respective demands for remodelling of the tendon and myofibre sides of the junction according to loading patterns. This insight refines our fundamental understanding of the human MTJ at the cell and structural levels.Competing Interest StatementThe authors have declared no competing interest.

Background: Plantar fasciitis is a painful tendinous condition (tendinopathy) with a high prevalence in athletes. While a healthy tendon has limited blood flow, ultrasound has indicated elevated blood flow in tendinopathy, but it is unknown if this is related to a de facto increase in the tendon vasculature. Likewise, an accumulation of glycosaminoglycans (GAGs) is observed in tendinopathy, but its relationship to clinical pain is unknown. Purpose: To explore to what extent vascularization, inflammation, and fat infiltration were present in patients with plantar fasciitis and if they were related to clinical symptoms. Study Design: Descriptive laboratory study. Methods: Biopsy specimens from tendinopathic plantar fascia tissue were obtained per-operatively from both the primary site of tendon pain and tissue swelling (“proximal”) and a region that appeared macroscopically healthy at 1 to 2 cm away from the primary site (“distal”) in 22 patients. Biopsy specimens were examined with immunofluorescence for markers of blood vessels, tissue cell density, fat infiltration, and macrophage level. In addition, pain during the first step in the morning (registered during an earlier study) was correlated with the content of collagen and GAGs in tissue. Results: High vascularization (and cellularity) was present in both the proximal (0.89%) and the distal (0.96%) plantar fascia samples, whereas inconsistent but not significantly different fat infiltration and macrophage levels were observed. The collagen content was similar in the 2 plantar fascia regions, whereas the GAG content was higher in the proximal region (3.2% in proximal and 2.8% in distal; P = .027). The GAG content in the proximal region was positively correlated with the subjective morning pain score in the patients with tendinopathy (n = 17). Conclusion: In patients with plantar fasciitis, marked tissue vascularization was present in both the painful focal region and a n

Background: Achilles tendon ruptures often result in long-term functional deficits despite accelerated (standard) rehabilitation. Purpose/Hypothesis: The purpose of this study was to investigate if delayed loading would influence functional, clinical, and structural outcomes of the muscles and tendon 1 year after a surgical repair. It was hypothesized that delaying the loading would reduce the heel-rise height deficit 1 year after Achilles tendon rupture. Study Design: Randomized controlled trial; Level of evidence, 1. Methods: In total, 48 patients with a surgically repaired Achilles tendon rupture were randomized to 2 groups: the standard group received the currently accepted rehabilitation, and the delayed group received the same rehabilitation except that initial loading was delayed by 6 weeks. The primary outcome was the heel-rise height difference between the injured and uninjured sides at 1 year. The secondary outcomes were (1) tendon length measured with magnetic resonance imaging, (2) muscle fascicle length and pennation angle of the gastrocnemius medialis muscle, (3) Doppler activity measured with ultrasonography, (4) Achilles tendon Total Rupture Score (ATRS), and (5) isometric muscle strength. Results: The mean heel-rise height deficits for the standard and delayed groups were −2.2 cm and −2.1 cm, respectively (P = .719). The soleus part of the tendon was already elongated 1 week after surgery in both groups without a between-group difference (side-to-side difference: standard, 16.3 mm; delayed, 17.5 mm; P = .997) and did not change over 52 weeks. The gastrocnemius tendon length was unchanged at 1 week but elongated over time without a between-group difference (side-to-side difference at 52 weeks: standard, 10.5 mm; delayed, 13.0 mm; P = .899). The delayed group had less Doppler activity at 12 weeks (P = .006) and a better ATRS (standard, 60 points; delayed, 72 points; P = .032) at 52 weeks. Conclusion: Delayed, Background: Achilles tendon ruptures often result in long-term functional deficits despite accelerated (standard) rehabilitation. Purpose/Hypothesis: The purpose of this study was to investigate if delayed loading would influence functional, clinical, and structural outcomes of the muscles and tendon 1 year after a surgical repair. It was hypothesized that delaying the loading would reduce the heel-rise height deficit 1 year after Achilles tendon rupture. Study Design: Randomized controlled trial; Level of evidence, 1. Methods: In total, 48 patients with a surgically repaired Achilles tendon rupture were randomized to 2 groups: the standard group received the currently accepted rehabilitation, and the delayed group received the same rehabilitation except that initial loading was delayed by 6 weeks. The primary outcome was the heel-rise height difference between the injured and uninjured sides at 1 year. The secondary outcomes were (1) tendon length measured with magnetic resonance imaging, (2) muscle fascicle length and pennation angle of the gastrocnemius medialis muscle, (3) Doppler activity measured with ultrasonography, (4) Achilles tendon Total Rupture Score (ATRS), and (5) isometric muscle strength. Results: The mean heel-rise height deficits for the standard and delayed groups were −2.2 cm and −2.1 cm, respectively (P =.719). The soleus part of the tendon was already elongated 1 week after surgery in both groups without a between-group difference (side-to-side difference: standard, 16.3 mm; delayed, 17.5 mm; P =.997) and did not change over 52 weeks. The gastrocnemius tendon length was unchanged at 1 week but elongated over time without a between-group difference (side-to-side difference at 52 weeks: standard, 10.5 mm; delayed, 13.0 mm; P =.899). The delayed group had less Doppler activity at 12 weeks (P =.006) and a better ATRS (standard, 60 points; delayed, 72 points; P =.032) at 52 weeks. Conclusion: Delayed loading was not superior to standard loading

The myotendinous junction (MTJ) is a specialized domain of the multinucleated myofibre that is faced with the challenge of maintaining robust cell–matrix contact with the tendon under high mechanical stress and strain. Here, we profiled 24,124 nuclei in semitendinosus muscle–tendon samples from three healthy males by using single-nucleus RNA sequencing (snRNA-seq), alongside spatial transcriptomics, to gain insight into the genes characterizing this specialization in humans. We identified a cluster of MTJ myonuclei represented by 47 enriched transcripts, of which the presence of ABI3BP, ABLIM1, ADAMTSL1, BICD1, CPM, FHOD3, FRAS1 and FREM2 was confirmed at the MTJ at the protein level in immunofluorescence assays. Four distinct subclusters of MTJ myonuclei were apparent, comprising two COL22A1-expressing subclusters and two subclusters lacking COL22A1 expression but with differing fibre type profiles characterized by expression of either MYH7 or MYH1 and/or MYH2. Our findings reveal distinct myonuclei profiles of the human MTJ, which represents a weak link in the musculoskeletal system that is selectively affected in pathological conditions ranging from muscle strains to muscular dystrophies.