Bone Abstracts

Osteoclasts are highly specialized cell types, responsible for the resorption of bone matrix. Coordinated with osteoblasts they contribute to a proper bone turnover. An impaired or reduced function of the osteoclast leads to a pathogenic increase of the bone mass and finally osteopetrosis. Lysosomal hydrolases, as exemplied by CTSK and Acp5 (TRAP), are known to play an important role in the function of osteoclasts, and knockout mouse models of these proteins develop a bone resorption phenotype. Apart from these soluble lysosomal enzymes, the importance of lysosomal membrane proteins in the osteoclast resorptive function such as CLC-7, OSTMN1 and ATP6a3 is characterized by the regulation of the conditions in the resorption lacuna. Mutations or knockout of these genes in human patients and mouse models, respectively, also lead to ostepetrotic phenotypes.

Due to the similarities between the ruffled border and the limiting membrane of the lysosome, it is of great interest to generally address the possible role of lysosomal membrane proteins in osteoclasts. MFSD1 and TMEM106b are two recently identified lysosomal membrane proteins, whose function has not been yet unravelled. Mfsd1 is a lysosomal transporter for so far unknown metabolite(s). The function of Tmem106b in osteoclasts is also unknown, but it possibly mediates the retrograde transport of lysosomes in neuronal dendrites.

MFSD1 is highly present in bone marrow macrophages, and its expression is upregulated upon stimulation with MCSF and RANKL, reaching its maximum after 3 days of treatment. MFSD1 is an unglycosylated protein. However, subcellular localization by immunofluorescence revealed the presence of MFSD1 in lysosomes in differentiated osteoclasts.

Analysis of osteoclasts differentiation from bone marrow and its capacity of resorption, using the KO mouse model for MFSD1 and TMEM106b will allow us to get a deeper insight of the importance of both proteins in osteoclast biology.