Mast cell inhibition as a therapeutic approach in fibrodysplasia ossificans progressiva (FOP)
TA Brennan, CM Lindborg, CR Bergbauer, H Wang… - Bone, 2018 - Elsevier
TA Brennan, CM Lindborg, CR Bergbauer, H Wang, FS Kaplan, RJ Pignolo
Bone, 2018•ElsevierBackground 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 …
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 …
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.
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