TY - JOUR
T1 - Mast cell inhibition as a therapeutic approach in fibrodysplasia ossificans progressiva (FOP)
AU - Brennan, Tracy A.
AU - Lindborg, Carter M.
AU - Bergbauer, Christian R.
AU - Wang, Haitao
AU - Kaplan, Frederick S.
AU - Pignolo, Robert J.
N1 - Publisher Copyright:
© 2017 Elsevier Inc.
PY - 2018/4
Y1 - 2018/4
N2 - Background: Episodic flare-ups of fibrodysplasia ossificans progressiva (FOP) are characterized clinically by severe, often posttraumatic, connective tissue swelling and intramuscular edema, followed histologically by an intense and highly angiogenic fibroproliferative reaction. This early inflammatory and angiogenic fibroproliferative response is accompanied by the presence of abundant mast cells far in excess of other reported myopathies. Results: Using an injury-induced, constitutively-active transgenic mouse model of FOP we show that mast cell inhibition by cromolyn, but not aprepitant, results in a dramatic reduction of heterotopic ossification. Cromolyn, but not aprepitant, significantly decreases the total number of mast cells in FOP lesions. Furthermore, cromolyn specifically diminishes the number of degranulating and resting degranulated mast cells in pre-osseous lesions. Conclusions: This work demonstrates that consideration of FOP as a type of localized mastocytosis may offer new therapeutic interventions for treatment of this devastating condition.
AB - Background: Episodic flare-ups of fibrodysplasia ossificans progressiva (FOP) are characterized clinically by severe, often posttraumatic, connective tissue swelling and intramuscular edema, followed histologically by an intense and highly angiogenic fibroproliferative reaction. This early inflammatory and angiogenic fibroproliferative response is accompanied by the presence of abundant mast cells far in excess of other reported myopathies. Results: Using an injury-induced, constitutively-active transgenic mouse model of FOP we show that mast cell inhibition by cromolyn, but not aprepitant, results in a dramatic reduction of heterotopic ossification. Cromolyn, but not aprepitant, significantly decreases the total number of mast cells in FOP lesions. Furthermore, cromolyn specifically diminishes the number of degranulating and resting degranulated mast cells in pre-osseous lesions. Conclusions: This work demonstrates that consideration of FOP as a type of localized mastocytosis may offer new therapeutic interventions for treatment of this devastating condition.
KW - ACVR1
KW - Cromolyn
KW - Fibrodyplasia ossificans progressiva (FOP)
KW - Heterotopic ossification
KW - Mast cells
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U2 - 10.1016/j.bone.2017.08.023
DO - 10.1016/j.bone.2017.08.023
M3 - Article
C2 - 28851540
AN - SCOPUS:85028617467
SN - 8756-3282
VL - 109
SP - 259
EP - 266
JO - Bone
JF - Bone
ER -