Abstract
The mechano-response of highly loaded tissues such as bones or tendons is well investigated, but knowledge regarding the mechano-responsiveness of adjacent tissues such as the subacromial bursa is missing. For a better understanding of the physiological role of the bursa as a friction-reducing structure in the joint, the study aimed to analyze whether and how bursa-derived cells respond to physiological and pathological mechanical loading. This might help to overcome some of the controversies in the field regarding the role of the bursa in the development and healing of shoulder pathologies. Cells of six donors seeded on collagen-coated silicon dishes were stimulated over 3 days for 1 or 4 h with 1, 5, or 10% strain. Orientation of the actin cytoskeleton, YAP nuclear translocation, and activation of non-muscle myosin II (NMM-II) were evaluated for 4 h stimulations to get a deeper insight into mechano-transduction processes. To investigate the potential of bursa-derived cells to adapt their matrix formation and remodeling according to mechanical loading, outcome measures included cell viability, gene expression of extracellular matrix and remodeling markers, and protein secretions. The orientation angle of the actin cytoskeleton increased toward a more perpendicular direction with increased loading and lowest variations for the 5% loading group. With 10% tension load, cells were visibly stressed, indicated by loss in actin density and slightly reduced cell viability. A significantly increased YAP nuclear translocation occurred for the 1% loading group with a similar trend for the 5% group. NMM-II activation was weak for all stimulation conditions. On the gene expression level, only the expression of TIMP2 was down-regulated in the 1 h group compared to control. On the protein level, collagen type I and MMP2 increased with higher/longer straining, respectively, whereas TIMP1 secretion was reduced, resulting in an MMP/TIMP imbalance. In conclusion, this study documents for the first time a clear mechano-responsiveness in bursa-derived cells with activation of mechano-transduction pathways and thus hint to a physiological function of mechanical loading in bursa-derived cells. This study represents the basis for further investigations, which might lead to improved treatment options of subacromial bursa-related pathologies in the future.
Highlights
Mechanical stimuli are known to be sensed especially by cells of mechanically highly loaded tissues, which are directly responsible for movement such as bones, tendons, and muscles
Digital image correlation revealed that applying 2, 4, 8, 10, and 16% of stroke to the silicon dish holder resulted in a 35–38% reduced strain magnitude on the surface area of the silicon dish in tensional direction
The overall results of the present study show that bursa-derived cells respond to mechanical signals and show specific reactions to distinct strain magnitudes
Summary
Mechanical stimuli are known to be sensed especially by cells of mechanically highly loaded tissues, which are directly responsible for movement such as bones, tendons, and muscles. For adjacent tissues that are only indirectly loaded, such mechanoresponsiveness has so far not been investigated One of these adjacent tissues is the subacromial bursa, which is responsible for reducing friction between the rotator cuff tendons and the acromion at the shoulder (Draghi et al, 2015). There exist currently several controversies in the field regarding the effectiveness of this procedure (Butt et al, 2015; Beard et al, 2017; Farfaras et al, 2018) It remains unclear if the subacromial bursa might have a regenerative capacity for surrounding tissues as it contains high amounts of growth factors, is highly vascularized, and contains stem cells (Steinert et al, 2015; Chillemi et al, 2016; Poldoja et al, 2017). The aim of the present study is to obtain a more detailed picture of the subacromial bursa by understanding the role of mechanical strain on bursa-derived cells
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