Regulation of lysosome biogenesis and functions in osteoclasts

Abstract

In order to resorb the mineralized bone extracellular matrix, the osteoclast relies on the generation of a resorption lacuna characterized by the presence of specific proteases and a low pH. Hence, bone resorption by osteoclasts is highly dependent on lysosomes, the organelles specialized in intra- and extracellular material degradation. This is best illustrated by the fact that multiple forms of human osteopetrosis are caused by mutations in genes encoding for lysosomal proteins. Yet, until recently, the molecular mechanisms regulating lysosomal biogenesis and function in osteoclasts were poorly understood. Here we review the latest developments in the study of lysosomal biogenesis and function in osteoclasts with an emphasis on the transcriptional control of these processes.

Keywords: PKCβ; RANKL; TFEB; bone resorption; lysosomal biogenesis; lysosome; osteoclast.

Figure 1. Lysosomal function, regulation, and biogenesis in osteoclasts. A bone-resorbing osteoclast is schematized. Proteins implicated in lysosomal biogenesis, in lysosomes trafficking and exocytosis, in ECM acidification, and in ECM degradation are indicated on the left. The recently identified pathway linking RANKL signaling, PKCβ, and TFEB to transcriptional regulation of lysosomal biogenesis is also included. See text for more details.