Cell-cell junctions in developing and adult tendons

Abstract

Tendons connect muscles to bones to transfer the forces necessary for movement. Cell-cell junction proteins, cadherins and connexins, may play a role in tendon development and injury. In this review, we begin by highlighting current understanding of how cell-cell junctions may regulate embryonic tendon development and differentiation. We then examine cell-cell junctions in postnatal tendon, before summarizing the role of cadherins and connexins in adult tendons. More information exists regarding the role of cell-cell junctions in the formation and homeostasis of other musculoskeletal tissues, namely cartilage and bone. Therefore, to inform future tendon studies, we include a brief survey of cadherins and connexins in chondrogenesis and osteogenesis, and summarize how cell-cell junctions are involved in some musculoskeletal tissue pathologies. An enhanced understanding of how cell-cell junctions participate in tendon development, maintenance, and disease will benefit future regenerative strategies.

Single-Cell Transcriptomics Analysis of the Pathogenesis of Tendon Injury

“…However, tendon healing is extremely slow and inefficient due to the lack of cellularity of the tendon tissue and growth factors, and the structural integrity and mechanical strength of the tendon are significantly inferior to the normal undamaged tendon [7][8][9]. Thus, the repair of tendon injury remains an immense challenge clinically, mainly due to the limited tendon healing capacity and our limited understanding of the underlying biology of tenocytes and the regulatory mechanisms of tendon injury occurrence [10].…”

Proteins Derived From MRL/MpJ Tendon Provisional Extracellular Matrix and Secretome Promote Pro-Regenerative Tenocyte Behavior

“…Moreover, we and others (53) have shown that connexin-43 localizes along tenocyte processes before assembling into cell-cell gap junctions at higher cell densities. Connexin-43 is the most abundant gap junction present in adult tendons, forming longitudinal and lateral contacts that regulate cellular metabolism, mechanosensitivity (e.g., stretch-induced calcium and ATP release), and intercellular communication through paracrine and autocrine effects (54)(55)(56). Taken together, these results suggest that early upregulation of connexin-43 activity through mitogenic stimulation with MRL/MpJ-derived components or the recombinant protein therapeutic facilitates an expedited healing response characterized by increased tenocyte proliferation, migration, and fibronectin deposition.…”

The LINC complex regulates Achilles tendon elastic modulus, Achilles and tail tendon collagen crimp, and Achilles and tail tendon lateral expansion during early postnatal development

“…It is well-established that mechanotransducive processes have critical roles in tenogenesis 19,31,58 , but many mechanotransducive tenogenic mechanisms remain enigmatic. Our work implicates Akt signaling 50 , and has summarized the role of mechanosensitive cell-cell junction proteins, particularly N-cadherin and Connexin-43 51 , on tenogenic MSCs and tendon cells, respectively. As LINC is a nuclear mechanostransducer and β-catenin/Akt modular, LINC’s potential regulatory role in tenogenesis warrants further investigation.…”