There have been three
publications on Netrin-1 at the ACR 2015 Annual Meeting in San Francisco. Netrin-1
plays a role in leukocyte function and inflammation or: “Netrin-1 is a
laminin-like matrix protein that acts as a chemorepulsant and which is
expressed during and required for osteoclast differentiation. In other settings
Netrin1 has been reported to play a pathogenic role during inflammation by
preventing macrophage egress from inflamed sites.” I like the word egress; I
guess Ira Tabas used it for the first time describing macrophage function. What
do the studies tell us?
Aranzazu Mediero and
colleagues presented: “Netrin-1 and Its Receptor Unc5b Are Novel Targets for
the Treatment of Inflammatory Arthritis.” Conclusion: “Blockade of Netrin-1 and
its receptor Unc5b by treatment, in vivo, with murine monoclonal antibodies
prevents bone destruction and K/BxN serum transfer-induced arthritis. Netrin-1
may be a novel therapeutic target for inflammatory bone destruction and other
forms of osteoclast-mediated bone resorption.” Which means, we could expect
from this principle a drug against erosive rheumatoid arthritis and would have
to look closely if inflammation per se would be reduced.
The second study was also
presented by Aranzazu Mediero: “Stimulation of the Adenosine A2A Receptor
(A2AR) Regulates the Expression of Netrin-1 (Ntn1) and Its Receptors (Unc5b,
DCC) and Inhibits Wear Particle-Induced Inflammatory Osteolysis in a Model of
Joint Prosthesis Loosening.” Conclusion: “Ntn1 expression on macrophages and OC
plays a central role in wear particle-induced osteolysis and adenosine A2AR
stimulation downregulates Ntn1expression and inhibits bony destruction at sites
of wear particle-induced osteolysis. Moreover, Ntn1-unc5b and A2AR stimulation
reciprocally diminish signaling by each other. These results suggest that
targeting Ntn1 directly or via stimulation of adenosine A2AR may be a novel
approach to prevent osteolysis and joint prosthesis loosening.”
Also the third study was presented
by Aranzazu Mediero: “Netrin-1 and Its Receptors Unc5b and DCC May be Useful
Targets for Preventing Multiple Myeloma Bone Lesions”. Conclusion: “Anti-netrin-1
and -Unc5b treatment decreases osteoclast formation in a murine model of
myeloma and decreases myeloma bone lesions. Targeting Netrin-1 or its receptor
Unc5b may be a novel therapeutic approach for multiple myeloma.”
The researchers around Aranzazu
Mediero presented data on Netrin-1, which showed to influence inflammatory bone
destruction and resorption. Netrin-1 might
be a target to treat rheumatoid arthritis as well as other diseases.
References:
Mediero A, Wilder T,
Cronstein B. Netrin-1 and Its Receptor Unc5b Are Novel Targets for the
Treatment of Inflammatory Arthritis [abstract]. Arthritis Rheumatol. 2015;
67 (suppl 10).
http://acrabstracts.org/abstract/netrin-1-and-its-receptor-unc5b-are-novel-targets-for-the-treatment-of-inflammatory-arthritis/.
Accessed December 11, 2015.
Mediero A, Ramkhelawon B,
Perez-Aso M, Moore K, Cronstein B. Stimulation of the Adenosine
A2A Receptor (A2AR) Regulates the Expression of Netrin-1 (Ntn1) and Its
Receptors (Unc5b, DCC) and Inhibits Wear Particle-Induced Inflammatory
Osteolysis in a Model of Joint Prosthesis Loosening [abstract]. Arthritis
Rheumatol. 2015; 67 (suppl 10).
http://acrabstracts.org/abstract/stimulation-of-the-adenosine-a2a-receptor-a2ar-regulates-the-expression-of-netrin-1-ntn1-and-its-receptors-unc5b-dcc-and-inhibits-wear-particle-induced-inflammatory-osteolysis-in-a-model-o/.
Accessed December 11, 2015.
Mediero A, Wilder T,
Cronstein B. Netrin-1 and Its Receptors Unc5b and DCC May be Useful Targets for
Preventing Multiple Myeloma Bone Lesions [abstract]. Arthritis Rheumatol. 2015;
67 (suppl 10). http://acrabstracts.org/abstract/netrin-1-and-its-receptors-unc5b-and-dcc-may-be-useful-targets-for-preventing-multiple-myeloma-bone-lesions/.
Accessed December 11, 2015.
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