TOB1 Deficiency Enhances the Effect of Bone Marrow-Derived Mesenchymal Stem Cells on Tendon-Bone Healing in a Rat Rotator Cuff Repair Model

Background/Aims: Effective wound-healing generally requires efficient re-vascularization after injury, ensuring sufficient supply with oxygen, nutrients, and various cell populations. While this applies to most tissues, tendons are mostly avascular in nature and harbor relatively few cells, probably contributing to their poor regenerative capacity. Considering the minimal vascularization of healthy tendons, we hypothesize that controlling angiogenesis in early tendon healing is beneficial for repair tissue quality and function. Methods: To address this hypothesis, Bevacizumab, a monoclonal antibody blocking VEGF-A signaling, was locally injected into the defect area of a complete tenotomy in rat Achilles tendon. At 28 days postsurgery, the defect region was investigated using immunohistochemistry against vascular and lymphatic epitopes. Polarization microscopy and biomechanical testing was used to determine tendon integrity and gait analysis for functional testing in treated vs non-treated animals. Results: Angiogenesis was found to be significantly reduced in the Bevacizumab treated repair tissue, accompanied by significantly reduced cross sectional area, improved matrix organization, increased stiffness and Young's modulus, maximum load and stress. Further, we observed an improved gait pattern when compared to the vehicle injected control group. Conclusion: Based on the results of this study we propose that reducing angiogenesis after tendon injury can improve tendon repair, potentially representing a novel treatment-option.

Section: Discussionmentioning

confidence: 94%

Bevacizumab Improves Achilles Tendon Repair in a Rat Model

Tempfer

Kaser-Eichberger

Lehner

et al. 2018

“…Light emitting diode (LED)-based therapy, a non-invasive biophysical therapy, has been widely and successfully used in clinical practice for several diseases, including arthritic pain [8], osteoarthritis [9], rheumatoid arthritis [10], skin rejuvenation [11], and wound healing [12,13]. Recent studies have already demonstrated that red LED irradiation has beneficial effects on bone marrow-derived MSCs (BMSCs) proliferation and differentiation.…”

Section: Introductionmentioning

confidence: 99%

Effects of Blue Light Emitting Diode Irradiation On the Proliferation, Apoptosis and Differentiation of Bone Marrow-Derived Mesenchymal Stem Cells

Yuan

Yan

Gong

et al. 2017

Background/Aims: Blue light emitting diodes (LEDs) have been proven to affect the growth of several types of cells. The effects of blue LEDs have not been tested on bone marrowderived mesenchymal stem cells (BMSCs), which are important for cell-based therapy in various medical fields. Therefore, the aim of this study was to determine the effects of blue LED on the proliferation, apoptosis and osteogenic differentiation of BMSCs. Methods: BMSCs were irradiated with a blue LED light at 470 nm for 1 min, 5 min, 10 min, 30 min and 60 min or not irradiated. Cell proliferation was measured by performing cell counting and EdU staining assays. Cell apoptosis was detected by TUNEL staining. Osteogenic differentiation was evaluated by ALP and ARS staining. DCFH-DA staining and γ-H2A.X immunostaining were used to measure intracellular levels of ROS production and DNA damage. Results: Both cell counting and EdU staining assays showed that cell proliferation of BMSCs was significantly reduced upon blue LED irradiation. Furthermore, treatment of BMSCs with LED irradiation was followed by a remarkable increase in apoptosis, indicating that blue LED light induced toxic effects on BMSCs. Likewise, BMSC osteogenic differentiation was inhibited after exposure to blue LED irradiation. Further, blue LED irradiation was followed by the accumulation of ROS

“…The interaction of TGF-βs/BMPs with TGF-β specific type 1 and type 2 or BMP serine/threonine kinase receptors initiates the signaling cascade via canonical (or Smad-dependent pathways) and non-canonical pathways (or Smad-independent signaling pathways) [50]. The TGF-β/BMP signaling pathway plays an important regulatory role in bone repair [51-56]. It is also confirmed to be involved in PEMF-induced osteogenesis.…”

Section: Underlying Signaling Pathwaysmentioning

confidence: 99%

Underlying Signaling Pathways and Therapeutic Applications of Pulsed Electromagnetic Fields in Bone Repair

Yuan

Xin

Jiang

2018

Pulsed electromagnetic field (PEMF) stimulation, as a prospective, noninvasive, and safe physical therapy strategy to accelerate bone repair has received tremendous attention in recent decades. Physical PEMF stimulation initiates the signaling cascades, which effectively promote osteogenesis and angiogenesis in an orchestrated spatiotemporal manner and ultimately enhance the self-repair capability of bone tissues. Considerable research progresses have been made in exploring the underlying cellular and subcellular mechanisms of PEMF promotion effect in bone repair. Moreover, the promotion effect has shown strikingly positive benefits in the treatment of various skeletal diseases. However, many preclinical and clinical efficacy evaluation studies are still needed to make PEMFs more effective and extensive in clinical application. In this review, we briefly introduce the basic knowledge of PEMFs on bone repair, systematically elaborate several key signaling pathways involved in PEMFs-induced bone repair, and then discuss the therapeutic applications of PEMFs alone or in combination with other available therapies in bone repair, and evaluate the treatment effect by analyzing and summarizing recent literature.