In vitro osteoclastogenesis from Gaucher patients' cells correlates with bone mineral density but not with Chitotriosidase

BONDAR, C.; MUCCI, J.; CRIVARO, A.; ORMAZABAL, M.; CECI, R.; OLIVERI, B.; GONZÁLEZ, D.; ROZENFELD, P.

BONE

ELSEVIER SCIENCE INC

Año: 2017 vol. 103 p. 262 - 269

8756-3282

Gaucher disease (GD) is caused by mutations on the gene encoding for the lysosomal enzymeglucocerebrosidase. Type I GD (GD1) patients present anemia, hepatosplenomegaly and bone alterations. Inspite of treatment, bone alterations in GD patients persist, including poor bone mineral density (BMD). Mechanismsleading to bone damage are not completely understood, but previous reports suggest that osteoclastsare involved. Chitotriosidase (CHIT) is the most reliable biomarker used in the follow up of patients, althoughits correlationwith bone status is unknown. The aimof thisworkwas to study the pro-osteoclastogenic potentialin patients and to evaluate its correlation with CHIT activity levels and clinical parameters. PBMCs from treatedpatients and healthy controls were cultured in the presence of M-CSF, and mature osteoclasts were counted.BMD, blood CHIT activity and serum levels of CTX, BAP, and cytokines were evaluated in patients. We foundthat blood CHIT activity and osteoclast differentiation were significantly increased in patients, but no correlationbetween them was observed. Interestingly, osteoclast numbers but not CHIT, presented a negative correlationwith BMD expressed as Z-score. CTX, BAP and serum cytokines involved in bone remodeling were found alteredin GD1 patients. These results showfor the first time a correlation between osteoclast differentiation and BMDinGD1 patients, supporting the involvement of osteoclasts in the bone pathology of GD1. Our results also suggestthat an altered immune response may play an important role in bone damage.