Ubiquitin-specific protease USP34 controls osteogenic differentiation and bone formation by regulating BMP2 signaling.

The osteogenic differentiation of mesenchymal stem cells (MSCs) is governed by multiple mechanisms. Growing evidence indicates that ubiquitin-dependent protein degradation is critical for the differentiation of MSCs and bone formation; however, the function of ubiquitin-specific proteases, the largest subfamily of deubiquitylases, remains unclear. Here, we identify USP34 as a previously unknown regulator of osteogenesis. The expression of USP34 in human MSCs increases after osteogenic induction while depletion of USP34 inhibits osteogenic differentiation. Conditional knockout of Usp34 from MSCs or pre-osteoblasts leads to low bone mass in mice. Deletion of Usp34 also blunts BMP2-induced responses and impairs bone regeneration. Mechanically, we demonstrate that USP34 stabilizes both Smad1 and RUNX2 and that depletion of Smurf1 restores the osteogenic potential of Usp34-deficient MSCs in vitro Taken together, our data indicate that USP34 is required for osteogenic differentiation and bone formation.

Neural regulation of mesenchymal stem cells in craniofacial bone: development, homeostasis and repair.

Mesenchymal stem cells endow various functions, including proliferation, multipotency, migration, etc. Craniofacial bones originate from the cranial neural crest and are developed mainly through intramembranous ossification, which are different from long bones. There are varied mesenchymal stem cells existing in the craniofacial bone, including Gli1 + cells, Axin2 + cells, Prx1 + cells, etc. Nerves distributed in craniofacial area are also derived from the neural crest, and the trigeminal nerve is the major sensory nerve in craniofacial area. The nerves and the skeleton are tightly linked spatially, and the skeleton is broadly innervated by sensory and sympathetic nerves, which also participate in bone development, homeostasis and healing process. In this review, we summarize mesenchymal stem cells located in craniofacial bone or, to be more specific, in jaws, temporomandibular joint and cranial sutures. Then we discuss the research advance concerning neural regulation of mesenchymal stem cells in craniofacial bone, mainly focused on development, homeostasis and repair. Discovery of neural regulation of mesenchymal stem cells may assist in treatment in the craniofacial bone diseases or injuries.