Research ArticleBone

Osteoclast-mediated bone resorption is controlled by a compensatory network of secreted and membrane-tethered metalloproteinases

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Science Translational Medicine  05 Feb 2020:
Vol. 12, Issue 529, eaaw6143
DOI: 10.1126/scitranslmed.aaw6143

Codependent deconstruction

Bone homeostasis encompasses a balancing act between formation of new bone and remodeling and resorption of existing bone. For patients with bone-wasting disorders such as osteoporosis, bone resorption predominates. To identify potential therapeutic targets in maladaptive bone resorption, Zhu et al. investigated mechanisms of collagenolytic activity in osteoclasts. They found that dual deletion of the matrix metalloproteinases MMP9 and MMP14 inhibited murine and human osteoclast activity, increased bone density, and prevented against pathogenic bone loss in mice. Dual targeting of MMP9 and MMP14 could potentially help treat bone-wasting diseases.

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