| In vivo stimulation of de novo collagen production caused by cross-linked hyaluronic acid dermal filler injections in photodamaged human skin. | |
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MedLine Citation:
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PMID: 17309996 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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OBJECTIVE: To determine whether endogenous synthesis of new extracellular matrix may contribute to the degree and duration of clinical benefits derived from cross-linked hyaluronic acid dermal filler injections. DESIGN: In vivo biochemical analyses after filler injections. SETTING: Academic referral center. PARTICIPANTS: Eleven healthy volunteers (mean age, 74 years) with photodamaged forearm skin. Interventions Filler and vehicle (isotonic sodium chloride) injected into forearm skin and skin biopsy specimens taken 4 and 13 weeks later. MAIN OUTCOME MEASURES: De novo synthesis of collagen, the major structural protein of dermal extracellular matrix, was assessed using immunohistochemical analysis, quantitative polymerase chain reaction, and electron microscopy. RESULTS: Compared with controls, immunostaining in skin receiving cross-linked hyaluronic acid injections revealed increased collagen deposition around the filler. Staining for prolyl-4-hydroxylase and the C-terminal and N-terminal epitopes of type I procollagen was enhanced at 4 and 13 weeks after treatment (P<.05). Gene expression for types I and III procollagen as well as several profibrotic growth factors was also up-regulated at 4 and 13 weeks compared with controls (P<.05). Fibroblasts in filler-injected skin demonstrated a mechanically stretched appearance and a biosynthetic phenotype. In vitro, fibroblasts did not bind the filler, suggesting that cross-linked hyaluronic acid is not directly stimulatory. CONCLUSIONS: Injection of cross-linked hyaluronic acid stimulates collagen synthesis, partially restoring dermal matrix components that are lost in photodamaged skin. We hypothesize that this stimulatory effect may be induced by mechanical stretching of the dermis, which in turn leads to stretching and activation of dermal fibroblasts. These findings imply that cross-linked hyaluronic acid may be useful for stimulating collagen production therapeutically, particularly in the setting of atrophic skin conditions. |
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Authors:
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Frank Wang; Luis A Garza; Sewon Kang; James Varani; Jeffrey S Orringer; Gary J Fisher; John J Voorhees |
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Publication Detail:
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Type: Controlled Clinical Trial; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Archives of dermatology Volume: 143 ISSN: 0003-987X ISO Abbreviation: Arch Dermatol Publication Date: 2007 Feb |
Date Detail:
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Created Date: 2007-02-20 Completed Date: 2007-03-16 Revised Date: 2008-03-17 |
Medline Journal Info:
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Nlm Unique ID: 0372433 Medline TA: Arch Dermatol Country: United States |
Other Details:
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Languages: eng Pagination: 155-63 Citation Subset: AIM; IM |
Affiliation:
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Department of Dermatology, University of Michigan Medical School, Ann Arbor, MI 48109, USA. frawang@umich.edu |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Aged Aged, 80 and over Arm Collagen Type I / drug effects*, metabolism Dermis / drug effects, metabolism, pathology Female Fibroblasts / drug effects, physiology Humans Hyaluronic Acid / administration & dosage, analogs & derivatives*, pharmacology Injections, Intradermal Male Middle Aged Skin Aging / drug effects*, pathology, physiology Tissue Inhibitor of Metalloproteinases / metabolism Transforming Growth Factors / metabolism |
| Grant Support | |
ID/Acronym/Agency:
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1K24 AR01259/AR/NIAMS NIH HHS; 5T32 AR007197/AR/NIAMS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Collagen Type I; 0/Restylane; 0/Tissue Inhibitor of Metalloproteinases; 76057-06-2/Transforming Growth Factors; 9004-61-9/Hyaluronic Acid |
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