Molecular studies in flexor tendon wound healing: The role of basic fibroblast growth factor gene expression

Chang, James; Most, Daniel; Thunder, Richard; Mehrara, Babak J.; Longaker, Michael T.; Lineaweaver, William C.

doi:10.1016/s0363-5023(98)80015-4

Cited by 139 publications

(85 citation statements)

References 18 publications

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“…32,33 Besides TGF-b1, other cytokines, such as basic fibroblast growth factor (bFGF), nuclear transcription factor kappaB (NF-kB), and insulin-like growth factor (IGF) can be induced by NO in wound healing and these cytokines may also play an important role in collagen synthesis. [34][35][36][37][38] In our study, we found dual effects of nitric oxide on tendon cells. High doses of exogenous NO (SNAP) (> or ¼ 800 mM) inhibited the collagen synthesis in cultured human tendon cells, but lower doses of SNAP enhanced 3 H-proline and collagenase sensitive 3 H-proline incorporation into the cells.…”

Section: Discussionmentioning

confidence: 88%

Nitric oxide enhances collagen synthesis in cultured human tendon cells

Xia

Szomor

Wang

et al. 2005

Journal Orthopaedic Research

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Collagen deposition is an important process that occurs during wound healing. We and others have shown that nitric oxide (NO) is important in tendon healing. The mechanisms whereby healing is enhanced are, however, undetermined. The aim of this study was to investigate whether NO could enhance collagen synthesis in cultured human tendon cells via exogenous NO and via an adenovirus containing the gene for inducible nitric oxide synthase (Ad-iNOS). Tendon cells from the torn edge of the tendons of patients undergoing rotator cuff repair surgery were cultured following collagenase digestion, and stimulated with exogenous NO (SNAP), transfected with Ad-iNOS, and treated with the NOS inhibitor, L-NMMA. Total protein and collagen synthesis were evaluated by 3 H-proline and collagenase sensitive 3 H-proline incorporation in human tendon cells. High doses of exogenous NO (SNAP) inhibited collagen synthesis. Lower doses enhanced total protein and collagen synthesis of the tendon cells. Ad-iNOS successfully transfected active iNOS into human tendon cells in vitro and also enhanced total protein and collagen synthesis of the tendon cells. The NOS inhibitor, L-NMMA, inhibited the effects of iNOS on the cells. Our studies show for first time that nitric oxide can enhance collagen synthesis in human tendon cells in vitro. These results may explain, in part, at least, the beneficial effects of NO donors in animal models and during the treatment of tendonopathies in human clinical trials. ß

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Section: Discussionmentioning

confidence: 88%

Nitric oxide enhances collagen synthesis in cultured human tendon cells

Xia

Szomor

Wang

et al. 2005

Journal Orthopaedic Research

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“…3,[15][16][17][18] Other studies have focused on molecular treatment of the flexor tendon injury to provide adhesion-free healing via the delivery of anti-scarring adjuvants that inhibit the effects of TGF-b and bFGF among other factors. [19][20][21][22][23] Despite their promise, these approaches remain experimental and have yet to yield a clinical application, 3 largely because our understanding of the molecular mechanisms involved in the formation of adhesions after flexor tendon injury and grafting remains incomplete. The novel mouse model of FDL tendon grafts offers a quantitative tool to not only examine the biomechanical aspects of flexor tendon grafts, but also to potentially elucidate the molecular events involved in repair and subsequent adhesion formation via the use of transgenic mouse models of gain and loss of function.…”

Section: Discussionmentioning

confidence: 99%

Adhesions in a murine flexor tendon graft model: Autograft versus allograft reconstruction

Hasslund

Jacobson

Dadali

et al. 2008

Journal Orthopaedic Research

120

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Reconstruction of flexor tendons often results in adhesions that compromise joint flexion. Little is known about the factors involved in the formation of flexor tendon graft adhesions. In this study, we developed and characterized a novel mouse model of flexor digitorum longus (FDL) tendon reconstruction with live autografts or reconstituted freeze-dried allografts. Grafted tendons were evaluated at multiple time points up to 84 days post-reconstruction. To assess the flexion range of the metatarsophalangeal joint, we developed a quantitative outcome measure proportional to the resistance to tendon gliding due to adhesions, which we termed the Gliding Coefficient. At 14 days post-grafting, the Gliding Coefficient was 29-and 26-fold greater than normal FDL tendon for both autografts and allografts, respectively (p < 0.001), and subsequently doubled for 28-day autografts. Interestingly, there were no significant differences in maximum tensile force or stiffness between live autograft and freeze-dried allograft repairs over time. Histologically, autograft healing was characterized by extensive remodeling and exuberant scarring around both the ends and the body of the graft, whereas allograft scarring was abundant only near the graft-host junctions. Gene expression of GDF-5 and VEGF were significantly increased in 28-day autografts compared to allografts and to normal tendons. These results suggest that the biomechanical advantages for tendon reconstruction using live autografts over devitalized allografts are minimal. This mouse model can be useful in elucidating the molecular mechanisms in tendon repair and can aid in preliminary screening of molecular treatments of flexor tendon adhesions. ß

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“…The mechanical loads and growth factors induce the synthesis of collagen and other ECM components by tenocytes [16]. Other studies have shown that tendon cells have an intrinsic healing capacity such as proliferation, migration into tendon core [10,17,22,24], and that both intrinsic tenocytes and extrinsic synovial cells expressed a range of inflammatory markers in response to injury [6,19]. Moreover, fibroblasts become activated to migrate into the damaged tissue and to differentiate into myofibroblasts that contribute to tissue repair during wound healing by cytokines and mechanical microenvironment [12].…”

Section: Discussionmentioning

confidence: 99%

Cell Migration after Synovium Graft Interposition at Tendon Repair Site

Hayashi

Zhao

et al. 2012

Hand (New York, N,Y.)

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Background We have recently reported that interpositional synovium grafts from tendon sheath have a potential to accelerate tendon healing when implanted at the repair site. The purpose of this study was to investigate the effect of orientation of the synovium after synovium graft transplantation, by comparing the ability of cells from the visceral and parietal surfaces to migrate into the tendon in a canine tissue culture model. Methods The synovium graft was placed within a complete tendon laceration, with either the visceral or parietal surface facing the proximal end of the lacerated tendon. The number of migrating cells was quantified by a cell migration assay. Qualitative immunohistochemistry and confocal laser microscopy were also used at day 10. Results Many labeled synovial cells were observed within the tendon to which the visceral surface of the synovium graft was facing. Migrated cells were also observed on the parietal side, but there were fewer cells compared to visceral surface cells. Migrating cells all expressed α-smooth muscle actin. Conclusion We found that graft orientation affected cell migration. Whether this finding has clinical significance awaits in vivo study.

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Molecular studies in flexor tendon wound healing: The role of basic fibroblast growth factor gene expression

Cited by 139 publications

References 18 publications

Nitric oxide enhances collagen synthesis in cultured human tendon cells

Nitric oxide enhances collagen synthesis in cultured human tendon cells

Adhesions in a murine flexor tendon graft model: Autograft versus allograft reconstruction

Cell Migration after Synovium Graft Interposition at Tendon Repair Site

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