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

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 bonealterations. In spite of treatment, bone alterations in GD patients persist, including poor BoneMineral Density (BMD). Mechanisms leading to bone damage are not completely understood,but previous reports suggest that osteoclasts are involved. Chitotriosidase (CHIT) is the mostreliable biomarker used in the follow up of patients, although its correlation with bone statusis unknown. The aim of this work was to study the pro-osteoclastogenic potential in patientsand to evaluate its correlation with CHIT activity levels and clinical parameters. PBMCs fromtreated patients and healthy controls were cultured in the presence of M-CSF, and matureosteoclasts were counted. BMD, blood CHIT activity and serum levels of CTX, BAP, andcytokines were evaluated in patients. We found that blood CHIT activity and osteoclastdifferentiation were significantly increased in patients, but no correlation between them wasobserved. Interestingly, osteoclast numbers but not CHIT, presented a negative correlationwith BMD expressed as Z-score. CTX, BAP and serum cytokines involved in bone remodelingwere found altered in GD1 patients. These results show for the first time a correlationbetween osteoclast differentiation and BMD in GD1 patients, supporting the involvement ofosteoclasts in the bone pathology of GD1. Our results also suggest that an altered immuneresponse may play an important role in bone damage.