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COMMENTARY BJD
British Journal of Dermatology
Osteopontin regulatory functions in the hair
follicle open a therapeutic approach for
hypertrichosis
DOI: 10.1111/bjd.18637
Linked Article: Alam et al. Br J Dermatol 2020; DOI:10.1111/
bjd.18479
Intact hair is a major factor for well-being. Not only hair loss
but also hypertrichosis or hirsutism causes distress. Hair follicles
are the reservoir for stem cells, which are essential in skin repair
and rejuvenation.
1
Therefore, one should avoid destroying hair
follicles when depleting unwanted hair. In this issue of the BJD,
Alam et al. test an engineered peptide derived from osteopontin,
named FOL-005, with the potential to deplete hair without
damaging the hair follicle stem cell pool.
2
Osteopontin is a versatile molecule expressed in different skin
compartments, with intracellular and extracellular functions.
3,4
It
promotes wound healing
5
and has inflammatory and regulatory
functions in skin disease such as psoriasis and contact dermatitis.
6,7
Signalling by osteopontin is mediated through various cell-surface
integrins and CD44.
8
It has long been recognized that osteopontin
is highly expressed in hair follicles.
9
In the rat hair follicle, osteo-
pontin is found only during the catagen phase in dermal papilla
cells, suggesting a role in the degenerative phase of the hair cycle.
10
Therefore, the authors tested the effects of the FOL-005 peptide on
the hair cycle, hypothesizing that osteopontin induces catagen, ini-
tiating hair loss. Through different in vitro and in vivo approaches
they describe that FOL-005 promotes premature catagen develop-
ment, but does not affect human hair follicle stem cells. Function-
ally, FOL-005 decreased transcription of the hair growth promotor
fibroblast growth factor-7 (FGF7), indicating that this pathway is
at least partially involved.
In this research paper, undiscovered functions of osteopontin
are revealed. By generating the recombinant FOL-005 peptide to
influence the effects of osteopontin, Alam et al. simultaneously elu-
cidate the functions of osteopontin and generate a molecule for
possible therapeutic use. Importantly, their finding that FOL-005
works at least partially by interfering with the signalling pathway
of the hair growth promotor FGF7 additionally opens the opportu-
nity for pathway modulation and further therapeutic intervention.
Their insights may be of interest not only to mimic osteopontin
function, but also to block osteopontin to inhibit hair loss.
However, further experiments are essential. The work was per-
formed in artificial systems that rely on human scalp skin, in
which great interindividual differences are present, possibly
explaining the variation of results. Furthermore, in the skin xeno-
transplant model the effects of mouse hormones, growth factors
and immune mediators cannot be excluded. As the model uses
human scalp skin it has to be examined whether hair follicles in
other locations are susceptible. Presently, dose titration experi-
ments for FOL-005 are lacking. FOL-005 is a peptide of 15 amino
acids that does not have the functional Arg-Gly-Asp sequence and
cannot interact with avb3 integrin, a major osteopontin receptor.
Experiments so far do not conclusively demonstrate through
which receptors the peptide exerts its effects, although FOL-005
seems to bind and signal through b1-integrins. Here, in-depth
research, for example with blocking antibodies, has to follow.
Alam et al. impressively demonstrate how molecular medi-
cine translates into the clinic to develop modern therapeutics.
In this case, there is hope for highly specific treatment of
hypertrichosis with few side-effects. Still, there is a long way
to go before routine use.
J.M. Weiss iD
Department of Dermatology and Allergy, University of Ulm,
Albert-instein-llee 23, D-lm, Germany
E-mail: johannes.weiss@uniklinik-ulm.de
Acknowledgments: Thanks to Mari L. Shinohara (Department
of Immunology, Duke University School of Medicine, NC,
U.S.A.) for her critical review of this commentary.
Conflicts of interest: none to declare.
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