Deletion of Mitogen-Activated Protein Kinase Phosphatase 1 Modifies the Response to Mechanical Bone Marrow Ablation in a Mouse Model

摘要

The maintenance of bone mass results from a delicate balance between bone formation by osteoblasts and bone resorption by osteoclasts. Understanding these processes is essential for the development of effective treatments for skeletal diseases. Mechanical bone marrow ablation provides a unique animal model to study bone repair and the roles of specific genes in this process. Ablation of marrow induces the formation of intramembranous bone in the medullary cavity, which is subsequently resorbed by osteoclasts. We used this model to ask whether mitogen-activated protein kinase (MAPK) phosphatase 1 (MKP1) affects the bone formed in response to marrow ablation. MKP1 is a negative regulator of MAPK signaling, which is essential for a wide variety of cellular mechanisms, including those critical for osteoblast and osteoclast function. At 10 d after mechanical bone marrow ablation, the femurs of male mkp1^+/+ and mkp1^−/− mice were compared with those of unoperated baseline mice by using radiography, peripheral quantitative computed tomography, and microcomputed tomography. Both genotypes developed increased bone mass after marrow ablation, but the increase was more pronounced in mkp1^−/− mice compared with mkp1^+/+ mice. These results indicate that MKP1 affects the bone formed in response to marrow ablation and suggest encouraging possibilities for the use of inhibitors of MKP1 to modulate bone repair.