biostudies-literatureShen SVANIH HHS511https://www.ebi.ac.uk/biostudies/studies/S-EPMC10135754biostudies-literatureUnknown12(4)We previously demonstrated that mice with targeted deletion of the leucine repeat rich kinase 1 (<i>Lrrk1</i>) gene were osteopetrotic due to the failure of osteoclasts to resorb bone. To determine how LRRK1 regulates osteoclast activity, we examined the intracellular and extracellular acidification with an acidotropic probe, acridine orange, in live osteoclasts on bone slices. We examined lysosome distribution in osteoclasts by localization of LAMP-2, cathepsin K, and v-ATPase by immunofluorescent staining with specific antibodies. We found that both vertical and horizontal cross-sectional images of the wild-type (WT) osteoclasts showed orange-staining of the intracellular acidic vacuoles/lysosomes dispersed to the ruffled border. By contrast, the LRRK1 deficient osteoclasts exhibited fluBiologyLeucine Repeat Rich Kinase 1 Controls Osteoclast Activity by Managing Lysosomal Trafficking and Secretion.PMC10135754RO1 AR078843, R21 AR072831IK6 BX005381Zeng CLiu EKSi MXing WMohan SShen SChen YVacher JZhao HfalseLeucine Repeat Rich Kinase 1 Controls Osteoclast Activity by Managing Lysosomal Trafficking and Secretion.We previously demonstrated that mice with targeted deletion of the leucine repeat rich kinase 1 (<i>Lrrk1</i>) gene were osteopetrotic due to the failure of osteoclasts to resorb bone. To determine how LRRK1 regulates osteoclast activity, we examined the intracellular and extracellular acidification with an acidotropic probe, acridine orange, in live osteoclasts on bone slices. We examined lysosome distribution in osteoclasts by localization of LAMP-2, cathepsin K, and v-ATPase by immunofluorescent staining with specific antibodies. We found that both vertical and horizontal cross-sectional images of the wild-type (WT) osteoclasts showed orange-staining of the intracellular acidic vacuoles/lysosomes dispersed to the ruffled border. By contrast, the LRRK1 deficient osteoclasts exhibited flu2023-01-01T00:00:00Z2023 Mar2025-04-04T11:05:21.83Z2025-04-04T11:05:21.83ZS-EPMC101357543710671210.3390/biology12040511