Coordinated expression of scleraxis and Sox9 genes during embryonic development of tendons and cartilage

Abstract

Embryonic development of tendons is in close association with that of cartilage and bone. Although these tissues are derived from mesenchymal progenitor cells which also give rise to muscle and fat, their fates clearly diverse in early embryonic stages. Transcription factors may play pivotal roles in the process of determination and differentiation of tendon cells as well as other cells in the skeletal system. Scleruxis, a basic helix-loop-helix (bHLH) type transcription factor, is expressed in mesenchymal progenitors that later form connective tissues including tendons. Sox9 is an HMG-box containing transcription factor, which is expressed at high levels in chondrocytes. We hypothesized that the two transcription factors regulate the fate of cells that interact with each other at the interface between the two tissues during divergence of their differentiation pathways. To address this point, we investigated .scleraxis and Sox9 mRNA expression during mouse embyogenesis focusing on the coordinated development of tendons and skeletons. In the early stage of mesenchymal tissue development at 10.5 d.p.c., sclcruxis and Sox9 transcripts were expressed in thc mesenchymal progenitor cells in the appendicular and axial mesenchyme. At 11.5 d.p.c., sclrraxis transcripts were observed in the mesenchymal tissue surrounding skeletal primordia which express SoxY. From this stage, scleruxis expression was closely associated with, but distinct from, formation of skeletal primordia. At 13.5 d.p.c., scleruxis was expressed broadly in the interface between muscle and skeletal primordia while Sox9 expression is confined within the early skeletal primordia. Then, at 15.5 d.p.c., .sc,lm/si.s transcripts were more restricted to tendons. These observations revealed the presence of temporal and spatial association of sc1wtr.vi.s expression during embryonic development of tendon precursor cells in close association with that of Sox9 expression in chondrogenic cells in skeletal tissues.

Anterior cruciate ligament-derived cells have high chondrogenic potential

“…In the early phase of embryonic development, the expressions of Scx and Sox9 are overlapped in sclerotome. However, Scx is reduced in the center of Sox9-expresssed sclerotome during the following development [27].…”

“…4B). Several authors have indicated that common mesenchymal precursor cells expressing both Sox9 and Scx are involved in the coordinated development of cartilages, tendons, and ligaments [27,28]. In the early phase of embryonic development, the expressions of Scx and Sox9 are overlapped in sclerotome.…”

Expression of Id2 in the developing limb is associated with zones of active BMP signaling and marks the regions of growth and differentiation of the developing digits

“…Indeed, Id2 has been involved in the control of cell fate decision between two different cell types in other model systems as the terminal differentiation of different lineages of haematopoietic cells from a common progenitor (Ikawa et al, 2001). Tendons develop in close association with cartilages, and scleraxis, an helix-loop-helix transcription factor promotes the specification of mesenchyme towards the tendon lineage (Asou et al, 2002, Brent et al, 2003. At least in the axial skeleton tendon and cartilaginous fates are alternative and cartilage differentiation is required to actively repress tendon development (Brent et al, 2005).…”

Emerging Ideas: Evaluation of Stem Cells Genetically Modified with Scleraxis to Improve Rotator Cuff Healing

“…Scx is a basic helix-loop-helix transcription factor that has been implicated in tendon development and regeneration [2,23,26]. Endogenous expression of Scx defines a zone between sclerotomal and myotomal cells in the developing somite, and persists throughout tendon formation in the mouse embryo [4,5,24,26].…”

“…Scx deficiency results in severe tendon defects in mice [21]. Scx also is believed to direct tendinous attachments to bone through its effects on chondrogenic lineage formation [2,4,20]. The simultaneous role for Scx in tendon and cartilage development suggests it has the potential to improve regeneration of the rotator cuff insertion site consisting of the tendon and its cartilaginous transition zone into the bone [6,8,12,17,25].…”