Background: The exact pathways of collagen remodeling in tendon tissue are not well understood. Therefore, we have established a 3D collagen gel system and studied the remodeling capacity of two different TSPC lines: young, Y-TSPC and aged/degenerative, A-TSPC. We specifically investigated the involvement of integrin receptors in the remodeling process. Methods: Y- and A-TSPC were derived from human Achilles tendon. RT-PCR was used to assess the expression of collagen-binding integrins. Integrins a1 and a11 were silenced by lentiviral delivery of shRNA in the Y-TSPC. Control-shRNA, a1-shRNA and a11-shRNA virus was given for 24h and then cells were selected with zeocin for 10 days. The integrin knockdown (KD) efficiency was assessed by quantitative PCR and western blotting. Last, time-lapse recording of gel contraction of Y-TSPC+con, Y-TSPC+a1KD, Y-TSPC+a11KD, and A-TSPC were performed. Results: Integrin a1 and a11 were significantly downregulated in A-TSPC. Therefore, to mimic the A-TSPC we carried out a1 and a11 KD in Y-TSPC. PCR and western blot validated very efficient KD. Analyses of collagen contraction revealed that Y-TSPC+a11KD had significant reduction in collagen contractibility comparable to A-TSPC phenotype. Regarding integrin a1, we found that this receptor had no effect on the contraction rate of TSPC. Thus, to our knowledge we have now identified for the first time a novel role of a11 integrin in tendon matrix remodeling, and a follow up analyses of the exact downstream cascade are on the way.

Introduction

Osteoarthritis (OA) is a slow progressive disease and a huge economic burden. A new target for therapy could be a growth factor treatment to prevent the loss of cartilage following injuries to the joint. BMP-7 is a promising candidate for such a novel therapy based on growth factors. In this study we combined the chondroprotective effects of BMP-7 with a novel thermosensitive hydrogel to prevent cartilage degeneration in a murine OA model.

Mobility plays an important role, in particular for patients with osteoporosis and after trauma surgery, both as an outcome and as treatment. Mobility is closely linked to the patient”s quality of life and exercise is a powerful additional treatment option. In order to be able to generate an evidence base to evaluate various surgical and non-surgical treatment options, objective measurements of patient mobility and exercise over a certain time period are needed. Wearables are a promising candidate, with obvious advantages compared to questionnaires and/or PROs. However, when extracting parameters with wearables, one often faces the problem of algorithms not performing well enough for special cases like slow gait speeds or impaired gait, as they typically appear in this patient group. We plan to further extend the applicability of the actibelt system (3D accelerometer, 100Hz), in particular to improve the measurement precision of real-world walking speed in slow and impaired walking. We are using a special measurement wheel including a rotating 3D accelerometer that allows to capture high quality real-world walking speed and distance measurements, and a mobile high resolution camera system. In a first block 20 patients with osteoporosis were included in the study at the Ludwigs-Maximilians-University”s Department of General, Trauma and Reconstructive Surgery in Munich, Germany and equipped with an actibelt. Patients were asked to walk as “normal” as possible, while wearing their usual apparel, in the building and outside the building. They climbed stairs and had to deal with all unexpected “stop and go” events that appear in real-world walking. Various gait parameters will be extracted from the recorded data and compared to the gold standard. We will then tune the existing algorithms as well as new algorithms (e.g. step detection based on continuous wavelet transformation) to explore potential improvements of both step detection and speed estimation algorithms. Further refinement and validation using real world data is warranted.