Exposure of a tendon extracellular matrix to synovial fluid triggers endogenous and engrafted cell death: A mechanism for failed healing of intrathecal tendon injuries.

This research article investigates the damaging effect of synovial fluid (the lubricating fluid in joints) on cells present in tendons, which could limit the effectiveness of tendon repair treatments and may explain the poor success rate of injury healing within the joint.

Research Goals and Methods

The objective of the study was to understand how synovial fluid impacts the cells within tendons. Primarily, the researchers focused on two types of cells: tendon-derived cells (TDCs) and mesenchymal stem cells (MSCs).

• The team used explants (tissue samples) from equine tendons, specifically the superficial digital flexor, which is extra-synovial (outside synovial sheath), and deep digital flexor tendons, both from compressed intra-synovial regions (inside the synovial sheath) and tensile extra-synovial regions.
• These tissue samples were then cultured in media containing autologous (from the same individual) or allogeneic (from another individual of the same species) synovial fluid.
• The researchers also used human hamstring explants, which were cultured in allogeneic synovial fluid.
• The viability of the explants was assessed by staining, while the proliferation of the cells was determined using alamarblue®, a cell viability reagent.
• The research team also performed immunohistochemical staining for the detection of apoptosis (programmed cell death) by assessing expression levels of caspase-3, -8, and -9 proteins.

Key Findings

The results of the study highlighted the detrimental impact of synovial fluid on the viability of tendon cells.

• Both autologous and allogeneic synovial fluid led to rapid cell death in equine and human tendons.
• Synovial fluid did not impact the viability of equine epitenon cells (cells surrounding tendons), or monolayer MSCs and TDCs.
• However, when MSCs and TDCs were engrafted into non-viable native tendon matrices, they died when cultured in synovial fluid.
• Levels of apoptosis-related proteins were greatest in superficial digital flexor tendon explants exposed to allogeneic synovial fluid.

Conclusion and Implications

The findings suggest that cells introduced into the synovial region for tendon lesion repair are likely to be considerably less effective, due to their vulnerability to the harmful effects of synovial fluid. This could be a key factor in explaining the poor success rate of intra-synovial tendon healing following injuries, which commonly involve damage to the epitenon (outer layer of tendon) and contact with synovial fluid. The study thus highlights the essential need for strategies that can protect these cells from the deleterious effects of synovial fluid to ensure better healing outcomes for intra-synovial tendon injuries.