Scleraxis is required for the growth of adult tendons in response to mechanical loading

Abstract

Scleraxis is a basic helix-loop-helix transcription factor that plays a central role in promoting tenocyte proliferation and matrix synthesis during embryonic tendon development.However, the role of scleraxis in the growth and adaptation of adult tendons is not known. We hypothesized that scleraxis is required for tendon growth in response to mechanical loading, and that scleraxis promotes the specification of progenitor cells into tenocytes. We conditionally deleted scleraxis in adult mice using a tamoxifen-inducible Cre-recombinase expressed from the Rosa26 locus (Scx Δ ), and then induced tendon growth in Scx + and Scx Δ adult mice via plantaris tendon mechanical overload. Compared to the wild type Scx + group, Scx Δ mice demonstrated blunted tendon growth. Transcriptional and proteomic analyses revealed significant reductions in cell proliferation, protein synthesis, and extracellular matrix genes and proteins. Our results indicate that scleraxis is required for mechanically-stimulated adult tendon growth by causing the commitment of CD146 + pericytes into the tenogenic lineage, and by promoting the initial expansion of newly committed tenocytes and the production of extracellular matrix proteins.

The tendon interfascicular basement membrane provides a vascular niche for CD146+ cell subpopulations

“…Proteins of interest for immunolabelling were selected based on their expression by tendon progenitor cell subpopulations in previous reports (Yin et al, 2016) and their predicted interactions in Equus caballus (NCBI taxid: 9796) using STRING (version 10.5) networkbased predictions for CD146 and LAMA4 (Szklarczyk et al, 2017;Gumucio et al, 2020).…”

“…In adult tissues, cell surface markers, such as CD44 and CD90 (THY1), are members of a number of canonical marker panels routinely used in the characterisation and isolation of specific stromal/stem cell populations (Horwitz et al, 2005;Morath et al, 2016). Recent studies have also reported resident CD146 populations in tendon (Yin et al, 2016;Gumucio et al, 2020). CD146 or melanoma adhesion molecule (MCAM; MUC18; Gicerin; OMIM:155735) is a transmembrane glycoprotein belonging to the IgG superfamily of cell adhesion molecules (Shih, 1999).…”