Cytokines in rotator cuff degeneration and repair.
ABSTRACT The pathogenesis of rotator cuff degeneration remains poorly defined, and the incidence of degenerative tears is increasing in the aging population. Rates of recurrent tear and incomplete tendon-to-bone healing after repair remain significant for large and massive tears. Previous studies have documented a disorganized, fibrous junction at the tendon-to-bone interface after rotator cuff healing that does not recapitulate the organization of the native enthesis. Many biologic factors have been implicated in coordinating tendon-to-bone healing and maintenance of the enthesis after rotator cuff repair, including the expression and activation of transforming growth factor-β, basic fibroblast growth factor, platelet-derived growth factor-β, matrix metalloproteinases, and tissue inhibitors of metalloproteinases. Future techniques to treat tendinopathy and enhance tendon-to-bone healing will be driven by our understanding of the biology of this healing process after rotator cuff repair surgery. The use of cytokines to provide important signals for tissue formation and differentiation, the use of gene therapy techniques to provide sustained cytokine delivery, the use of stem cells, and the use of transcription factors to modulate endogenous gene expression represent some of these possibilities.
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ABSTRACT: I. The rabbit flexor tendon within the synovial sheath contains segments with fibrocartilage-like areas. These segments have a higher proteoglycan and a lower collagen and non-collagen protein synthesis compared to the segment with "true" tendon tissue. Cell proliferation is also lower within the proximal segment than in the intermediate and distal segments. These regional variations should be considered when interpreting experimental data. They may also be of importance for the variable healing capacity of different flexor tendon regions. II. Recombinant human insulin-like growth factor, insulin and fetal calf serum stimulate matrix synthesis and cell proliferation in a dose dependent manner in flexor tendon explants cultured for three days. rhIGF-I was more potent than insulin in stimulating cell proliferation and matrix synthesis. rhIGF-I also stimulated matrix synthesis to a higher degree than FCS. III. In long-term culture of flexor tendon explants, the addition of rhIGF-I to the culture medium stimulates matrix synthesis, but does not influence turn-over rates. The total hexosamine and collagen contents in tendons cultured in medium with rhIGF-I remain at the same level, while non-collagen protein content decreases. There are no major differences in matrix metabolism between tendons cultured in medium supplemented with FCS or with rhIGF-I only. rhIGF-I may therefore be used as a growth factor supplement in serum-free culture of tendon tissue. IV. Dehydration inhibits in vitro matrix synthesis and cell proliferation in tendon explants. These effects are counteracted by keeping the exposed tendon segments moist with physiological saline solution during preparation. The sensitivity of tendon tissue to dehydration should be considered during tendon surgery. V. Tendon explants, cultured in a diffusion chamber, survive and exhibit an intrinsic capacity for healing. In healing tendon segments incubated for three weeks, protein synthesis remains unchanged and collagen synthesis decreases, whereas the rate of cell proliferation increases as compared with native tendons. VI. Endotenon cells of the rabbit flexor tendon can restore the injured tendon surface and bridge the tendon gap. The rabbit flexor tendon is a morphologically and biochemically heterogeneous tissue with an intrinsic capability for healing. Tendon tissue is susceptible to dehydration and during exposure quickly looses its viability. The metabolic and proliferative capacity of the tendon is stimulated by growth factors and rhIGF-I may be of importance in tendon healing.Scandinavian journal of plastic and reconstructive surgery and hand surgery. Supplementum. 02/1991; 23:1-51.
Article: Recombinant human insulin-like growth factor-I stimulates in vitro matrix synthesis and cell proliferation in rabbit flexor tendon.[show abstract] [hide abstract]
ABSTRACT: Flexor tendons have an intrinsic ability for repair, with a capacity to metabolize matrix components and to proliferate. To identify factors with the potential of affecting those abilities, the effects of recombinant human insulin-like growth factor (rhIGF-I), insulin and fetal calf serum (FCS) on the synthesis of proteoglycan, collagen, and non-collagen protein and cell proliferation were investigated in short-term explant cultures of the deep flexor tendon of the rabbit. Matrix synthesis and cell proliferation were stimulated dose dependently by rhIGF-I at doses between 10 and 250 and at 10-100 ng/ml, respectively, by insulin at 250-5,000 ng/ml, and by FCS at 2-15%. Estimated maximal stimulation (Emax) of up to three times the control value was observed with rhIGF-I at 250 ng/ml. Maximal stimulation was observed at 5,000 ng/ml with insulin, and FCS at 15%. rhIGF-I was more potent than insulin in stimulating protein synthesis and cell proliferation. The Emax of stimulation of proteoglycan and collagen synthesis by rhIGF-I were two times that of FCS, and the Emax of cell proliferation by FCS was twice that of rhIGF-I. Growth factors thus have the ability to stimulate matrix synthesis and cell proliferation in rabbit flexor tendon. This provides a rationale for further studies on the role of growth factors in flexor tendon healing in humans.Journal of Orthopaedic Research 08/1991; 9(4):495-502. · 2.81 Impact Factor
Acta chirurgica Scandinavica. Supplementum 02/1959; 116(Supp 239):1-51.