Research Article| Volume 7, ISSUE 3, P202-209, June 1994

Correlation of proteolytic activities of organ cultured intact mouse skin with defined hair cycle stages

      This paper is only available as a PDF. To read, Please Download here.


      The cyclic growth activity of the hair follicle is characterized by substantial remodelling of the extracellular matrix, yet, little is known about the proteolytic activities regulating this process. In murine skin, hair cycling is highly synchronized and is associated with dramatic remodelling of all skin compartments. We therefore have assessed, in this pilot study, proteolytic activities of murine skin from various stages of the depilation-induced hair cycle. We show that the defined proteolytic activities displayed by organ cultured intact mouse skin differ between hair cycle stages. Skin with all follicles in telogen or mid anagen displayed only minimal lysis of collagen type I gels, while early anagen skin had significant collagenase activity. Skin cultured on gelatin gels at the air-liquid interphase (‘histoculture’) completely lysed the gel within 5 days when all follicles were in early anagen, while this was not observed with mid and very lateanagen skin. Zymography of conditioned medium from these cultures revealed the secretion of activated interstitial collagenase and of gelatinases of 72 and 92 kDa, with the maximum of interstitial collagenase activity secreted by anagen IV skin. Addition of TPA or TNF-α to the culture medium stimulated secreted collagenase type I activity. The C 57 BL-6 mouse offers an attractive model for dissecting and manipulating hair cycle-associated proteolysis in a physiologically relevant system.


      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Journal of Dermatological Science
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


      1. Ogawa H Lazarus GS Hopsu-Havu VK Biological role of proteinases and their inhibitors in skin. University of Tokyo Press, Tokyo1985
        • Lazarus GS
        • Schechter N
        • Jensen PJ
        • Fräki J
        Proteinase metabolism in human skin: the role of plasminogen activator and mast cell proteinases in cutaneous biology.
        in: Goldsmith LA Physiology, Biochemistry and Molecular Biology of the Skin. Oxford University Press, New York1991: 462-480
        • Bauer E
        • Goldberg GI
        • Eisen AZ
        • Welgus HG
        in: Goldsmith LA Physiology, Biochemistry, and Molecular Biology of the Skin. Oxford University Press, New York1991: 509-529
        • Paus R
        • Link RE
        The psoriatic epidermal lesion and anagen hair growth may share the same “switch-on” mechanism.
        Yale J Biol Med. 1988; 61: 467-476
        • Couchman JR
        • King JL
        • McCarthy KJ
        Distribution of two membrane proteoglycans through hair follicle development and the hair growth cycle.
        J Invest Dermatol. 1990; 94: 64-70
        • Westgate GE
        • Messenger AG
        • Watson LP
        • Gibson WT
        Distribution of proteoglycans during the hair growth cycle in human skin.
        J Invest Dermatol. 1991; 96: 191-195
      2. Stenn KS Messenger AG Baden HP The molecular and structural biology of hair. Ann NY Acad Sci. 642. 1991: 1-519
        • Link RE
        • Paus R
        • Stenn KS
        • Kuklinska E
        • Moellmann G
        Epithelial growth by rat vibrissae follicles in vitro requires mesenchymal contact via native extracellular matrix.
        J Invest Dermatol. 1990; 95: 202-207
        • Paus R
        • Czarnetzki BM
        Neue Perspektiven in der Haarforschung: auf der Suche nach der “biologischen Uhr” des Haarzyklus.
        Hautarzt. 1992; 43: 264-271
        • Chase HB
        Growth of the hair.
        Physiol Rev. 1954; 34: 113-126
        • Hansen LS
        • Coggle JE
        • Wells J
        • Charles MW
        The influence of the hair cycle on the thickness of mouse skin.
        Anat Rec. 1984; 210: 569-573
        • Paus R
        • Stenn KS
        • Link RE
        Telogen skin contains an inhibitor of hair growth.
        Br J Dermatol. 1990; 122: 777-784
        • Li L
        • Paus R
        • Margolis LB
        • Hoffman RM
        Hair growth in vitro from histocultured mouse skin.
        In Vitro Cell Dev Biol. 1992; 28A: 479-481
        • Li L
        • Paus R
        • Slominski A
        • Hoffman RM
        Skin histoculture assay for studying the hair cycle.
        In Vitro Cell Dev Biol. 1992; 28A: 695-698
        • Slominski A
        • Paus R
        • Costantino R
        Differential expression and activity of melanogenesis-related proteins during induced hair growth in mice.
        J Invest Dermatol. 1991; 96: 172-179
        • Li L
        • Margolis LB
        • Paus R
        • Hoffman RM
        Hair shaft elongation, follicle growth, and spontaneous regression in long-term gelatine sponge-supported histoculture of human scalp skin.
        in: Proc Natl Acad Sci USA. 89. 1992: 8764-8768
        • Dayer JM
        • Beutler B
        • Cerami A
        Cachectin/tumor necrosis factor stimulates collagenase and prostaglandin E2 production by human synovial cells and dermal fibroblasts.
        J Exp Med. 1985; 162: 2163-2168
        • Okada Y
        • Tsuchiya H
        • Shimizu H
        • et al.
        Induction and stimulation of 92 kDa gelatinase/type IV collagenase production in osteosarcoma and fibrosarcoma cell lines by tumor necrosis factor α.
        Biochem Biophys Res Commun. 1990; 171: 610-617
        • Unemori EN
        • Werb Z
        Reorganisation of polymerized actin: a possible trigger for induction of procollagenase.
        J Cell Biol. 1986; 103: 1021-1031
        • Masure S
        • Opdenaker G
        Cytokine-mediated proteolysis in tissue remodelling.
        Experientia. 1989; 45: 542-549
        • Laiho M
        • Keski-Oja J
        Growth factors in the regulation of pericellular proteolysis.
        Cancer Res. 1989; 49: 2533-2553
        • Argyris TS
        Hair growth induced by damage.
        Adv Biol Skin. 1967; 9: 339-356
        • Kawabe TT
        • Rea TJ
        • Flenniken AM
        • Williams BRG
        • Groppi VE
        • Buhl AE
        Loalization of TIMP in cycling mouse hair.
        Development. 1991; 111: 877-879
        • Nomura S
        • Hogan BLM
        • Willis AJ
        • Heath JK
        • Edwards DR
        Developmental expression of tissue inhibitor of metalloproteinase (TIMP) RNA.
        Development. 1989; 105: 575-583
        • Brenner CA
        • Adler RR
        • Rappolee DA
        • Pedersen RA
        • Werb Z
        Genes for extracellular matrix-degrading metalloproteinases and their inhibitor, TIMP, are expressed during early embryonal mammalian development.
        Genes Dev. 1989; 3: 848-859
      3. Orfanos CE Happle R Hair and Hair Diseases. Springer, Berlin1990
        • Rogers G
        • Martinet N
        • Steinert P
        • et al.
        Cultivation of murine hair follicles as organoids in a collagen matrix.
        J Invest Dermatol. 1987; 89: 369-379
        • Weinberg WC
        • Brown PD
        • Stetler-Stevenson WG
        • Yuspa SH
        Growth factors specifically alter hair follicle cell proliferation and collagenolytic activity alone or in combination.
        Differentiation. 1990; 45: 168-178
        • Gilbert SF
        Developmental Biology. Sinauer, Sunderland, MA1991
        • Li L
        • Margolis LB
        • Lishko VK
        • Hoffman RM
        Product-delivering liposomes specifically target the hair follicles in histocultured intact skin.
        In Vitro Cell Dev Biol. 1992; 28A: 679-681
        • Li L
        • Lishko V
        • Hoffman RM
        Liposome targeting of high molecular weight DNA to the hair follicles of histocultured skin: a model for gene therapy of the hair growth processes.
        In Vitro Cell Dev Biol. 1993; 29A: 258-260
        • Liotta L
        • Steeg PS
        • Stetler-Stevenson WG
        Cancer metastasis and angiogenesis: an imbalance of positive and negative regulation.
        Cell. 1991; 64: 327-336