Pim1 promotes the maintenance of bone homeostasis by regulating osteoclast function

Abstract

The Pim1 (proviral integration site for Moloney leukemia virus 1) protein is a serine/threonine kinase that is essential for cell proliferation, apoptosis and innate immune responses. Here we show that Pim1 promotes osteoclast resorptive function without affecting osteoclast numbers. Specifically, we found that mice lacking Pim1 (Pim1−/−) developed increased trabecular bone mass and indices such as trabecular bone-mass density. This was due to the direct phosphorylation of TRAF6 by Pim1 in mature osteoclasts, which activated the Akt–GSK3β signaling pathway. This, in turn, promoted the acetylation and consequent stabilization of microtubules, which permitted the formation of the osteoclast sealing zone. In vivo experiments then showed that, when mice with lipopolysaccharide-induced bone loss or tumor-induced osteolysis were treated with SGI-1776, a Pim1 inhibitor that is more selective for Pim1, the bone loss was significantly ameliorated. Thus, Pim1 plays an important role in osteoclast function and may be a therapeutic target for bone-related diseases. This study explores how a protein called Pim1 affects bone health. Bones constantly renew themselves through a process involving cells called osteoclasts, which break down old bone, and osteoblasts, which build new bone. When this balance is disrupted, it can lead to diseases such as osteoporosis. Researchers found that Pim1, a type of enzyme, plays a role in this process by affecting the stability of structures within osteoclasts called microtubules. The study used mice that lacked Pim1 and found they had stronger bones due to reduced bone breakdown. This was linked to changes in microtubule stability, influenced by Pim1 through a pathway involving other proteins, including Akt and TRAF6. The researchers also tested a drug called SGI-1776, which inhibits Pim1, and found that it could protect against bone loss in conditions such as inflammation and cancer. This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.