Mechanical Loading Improves Tendon-Bone Healing in a Rabbit Anterior Cruciate Ligament Reconstruction Model by Promoting Proliferation and Matrix Formation of Mesenchymal Stem Cells and Tendon Cells

Song, Frank M.; Jiang, Dawei; Wang, Tianchen; Wang, Yi; Chen, Fengmei; Xu, Guoxing; Kang, Yifan; Zhang, Yinquan

doi:10.1159/000460005

Cited by 71 publications

(34 citation statements)

References 56 publications

(60 reference statements)

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“…Mechanical loading plays an important role in regulating skeletal tissue homeostasis; thus, a number of studies have been conducted to investigate the effects of mechanical stimulation on skeletal cells, including osteoblasts, chondrocytes, skeletal muscle cells, and endothelial cells. It has been shown previously that cell proliferation of human tendon cells [22], as well as venous smooth muscle cells [23], was improved by cyclic stretch. In this study, we treated cells with longitudinal stretch with 2.5% and 5% magnitude to mimic physiological loading and found that appropriate mechanical stimulation increased cell proliferation of BM-MSCs.…”

Section: Discussionmentioning

confidence: 99%

Mechanical stretch induces antioxidant responses and osteogenic differentiation in human mesenchymal stem cells through activation of the AMPK-SIRT1 signaling pathway

Chen¹,

Yan

et al. 2018

Free Radical Biology and Medicine

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Mesenchymal stem cells (MSCs) are promising cell sources for regenerative medicine. Growing evidence has indicated that mechanical stimuli are crucial for their lineage-specific differentiation. However, the effect of mechanical loading on redox balance and the intracellular antioxidant system in MSCs was unknown. In this study, human bone marrow-derived MSCs (BM-MSCs) were subjected to cyclic stretch at the magnitude of 2.5%, 5%, and 10%. Cell proliferation, intracellular reactive oxygen species (ROS), expression of antioxidant enzymes, and osteogenic differentiation were evaluated. RNA was extracted and subjected to DNA microarray analysis. Sirtinol and compound C were used to investigate the underlying mechanisms involved silent information regulator type 1 (SIRT1) and AMP-activated protein kinase (AMPK). Our results showed that mechanical stretch at appropriate magnitudes increased cell proliferation, up-regulated extracellular matrix organization, and down-regulated matrix disassembly. After 3 days of stretch, intracellular ROS in BM-MSCs were decreased but the levels of antioxidant enzymes, especially superoxide dismutase 1 (SOD1), were up-regulated. Osteogenesis was improved by 5% stretch rather than 10% stretch, as evidenced by increased matrix mineralization and osteogenic marker gene expression. The expression of SIRT1 and phosphorylation of AMPK were enhanced by mechanical stretch; however, inhibition of SIRT1 or AMPK abrogated the stretch-induced antioxidant effect on BM-MSCs and inhibited the stretch-mediated osteogenic differentiation. Our findings reveal that mechanical stretch induced antioxidant responses, attenuated intracellular ROS, and improved osteogenesis of BM-MSCs. The stretch-induced antioxidant effect was through activation of the AMPK-SIRT1 signaling pathway. Our findings demonstrated that appropriate mechanical stimulation can improve MSC antioxidant functions and benefit bone regeneration.

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Section: Discussionmentioning

confidence: 99%

Mechanical stretch induces antioxidant responses and osteogenic differentiation in human mesenchymal stem cells through activation of the AMPK-SIRT1 signaling pathway

Chen¹,

Yan

et al. 2018

Free Radical Biology and Medicine

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“…Mechanical force may influence the healing potential as well. Song et al 22 demonstrated in a rabbit ACL reconstruction model that proliferation and differentiation of local precursor cells could be enhanced by mechanical stimulation. The relative low potential in the reattachment group assessed in this study may reflect the healing potential after mechanical stimulation of the attached cells.…”

Section: Discussionmentioning

confidence: 99%

The Influence of Ruptured Scar Pattern on the Healing Potential of Anterior Cruciate Ligament Remnant Cells

et al. 2018

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“…This could be significant because this would alter the strain through the graft, and tendon-bone healing is influenced by changes in ACL graft force with joint motion. 40 , 41 The decision to evaluate suspensory fixation was made based on its popular usage in the UK, but the fact that suspensory fixation is popular does not necessarily mean it is the correct fixation to use. For instance, the use of interference screw fixation in both the femoral and tibial tunnel has been shown to have good results 15 years postoperatively with respect to objective and subjective outcomes, and to ligamentous stability.…”

Section: Discussionmentioning

confidence: 99%

Decellularized porcine xenograft for anterior cruciate ligament reconstruction

Hexter

Hing

Haddad

et al. 2020

Bone & Joint Research

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Aims To evaluate graft healing of decellularized porcine superflexor tendon (pSFT) xenograft in an ovine anterior cruciate ligament (ACL) reconstruction model using two femoral fixation devices. Also, to determine if pSFT allows functional recovery of gait as compared with the preoperative measurements. Methods A total of 12 sheep underwent unilateral single-bundle ACL reconstruction using pSFT. Two femoral fixation devices were investigated: Group 1 (n = 6) used cortical suspensory fixation (Endobutton CL) and Group 2 (n = 6) used cross-pin fixation (Stratis ST). A soft screw was used for tibial fixation. Functional recovery was quantified using force plate analysis at weeks 5, 8, and 11. The sheep were euthanized after 12 weeks and comprehensive histological analysis characterized graft healing at the graft-bone interface and the intra-articular graft (ligamentization). Results The pSFT remodelled into a ligament-like structure and no adverse inflammatory reaction was seen. The ground reaction force in the operated leg of the Endobutton group was higher at 11 weeks (p < 0.05). An indirect insertion was seen at the graft-bone interface characterized by Sharpey-like fibres. Qualitative differences in tendon remodelling were seen between the two groups, with greater crimp-like organization and more aligned collagen fibres seen with Endobutton fixation. One graft rupture occurred in the cross-pin group, which histologically showed low collagen organization. Conclusion Decellularized pSFT xenograft remodels into a ligament-like structure after 12 weeks and regenerates an indirect-type insertion with Sharpey-like fibres. No adverse inflammatory reaction was observed. Cortical suspensory femoral fixation was associated with more enhanced graft remodelling and earlier functional recovery when compared with the stiffer cross-pin fixation.

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Mechanical Loading Improves Tendon-Bone Healing in a Rabbit Anterior Cruciate Ligament Reconstruction Model by Promoting Proliferation and Matrix Formation of Mesenchymal Stem Cells and Tendon Cells

Cited by 71 publications

References 56 publications

Mechanical stretch induces antioxidant responses and osteogenic differentiation in human mesenchymal stem cells through activation of the AMPK-SIRT1 signaling pathway

Mechanical stretch induces antioxidant responses and osteogenic differentiation in human mesenchymal stem cells through activation of the AMPK-SIRT1 signaling pathway

The Influence of Ruptured Scar Pattern on the Healing Potential of Anterior Cruciate Ligament Remnant Cells

Decellularized porcine xenograft for anterior cruciate ligament reconstruction

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