A molecular mechanism that promotes bone destruction could be harnessed to combat osteoporosis, suggests a paper online this week in Nature Medicine.
Bone formation depends on a balance between cells that create it―osteoblasts―and cells that destroy it―osteoclasts. Understanding the mechanisms that control the origin and function of these cells is crucial for developing treatments for diseases such as osteoporosis.
Kurt Redlich and colleagues report that the C-C chemokine receptor-2 (CCR2) is crucially involved in the regulation of bone mass by promoting the appearance of osteoclasts. The group found that mice lacking CCR2 have high bone mass owing to a decrease in number, size and function of osteoclasts. At the molecular level, activation of CCR2 in osteoclast progenitor cells results in increased expression of a molecule known as RANK, which enabled these cells to respond to signals that drive osteoclast differentiation.
In a model of postmenopausal osteoporosis―mice that underwent ovary removal and therefore have less oestrogen―CCR2 levels increased, thereby increasing RANK and the differentiation potential of osteoclast progenitor cells. As a result, mice lacking CCR2 are resistant to bone loss associated with reduced oestrogen. CCR2 activation could therefore be a target to combat postmenopausal osteoporosis.