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Inhibition of osteoclastogenesis by mechanically stimulated osteoblasts is attenuated during estrogen deficiency
H. Allison and L. M. McNamara
Am J Physiol Cell Physiol, 2019. doi: 10.1152/ajpcell.00168.2019.
Osteo- porotic bone loss and fracture have long been regarded to arise upon depletion of circulating estrogen, which increases osteoclastogenesis and bone resorption. Osteoblasts from human osteoporotic patients also display deficient osteogenic responses to mechanical loading. However, while osteoblasts play an important role in regulating osteoclast differentiation, how this relationship is affected by estrogen deficiency is unknown. This study seeks to determine how mechani- cally stimulated osteoblasts regulate osteoclast differentiation and matrix degradation under estrogen deficiency. Here, we report that osteoblast-induced osteoclast differentiation (indicated by tartrate- resistant acid phosphatase, cathepsin K, and nuclear factor of acti- vated T cells, cytoplasmic 1) and matrix degradation were inhibited by estrogen treatment and mechanical loading. However, estrogen-defi- cient osteoblasts exacerbated osteoclast formation and matrix degra- dation in conditioned medium and coculture experiments. This was accompanied by higher expression of cyclooxygenase-2 and macro- phage colony-stimulating factor, but not osteoprotegerin, by osteo- blasts under estrogen deficiency. Interestingly, this response was exacerbated under conditions that block the Rho-Rho-associated pro- tein kinase signaling pathway. This study provides an important, but previously unrecognized, insight into bone loss in postmenopausal osteoporosis, whereby estrogen-deficient osteoblasts fail to produce inhibitory osteoprotegerin after mechanical stimulation but upregulate macrophage colony-stimulating factor and cyclooxygenase-2 expres- sion and, thus, leave osteoclast activity unconstrained.
Full text of Dr H. Allison’s article is available from HERE
National University of Ireland Galway, Ireland.
Niloufar ‘ Nil ‘ Ansari
Monash University, Australia.