LOX Fails to Substitute for RANKL in Osteoclastogenesis

One of the hallmarks of scientific study is to never be satisfied. Even when a problem appears to be solved, there is always a reason to question it and to see if a better solution cannot be found. When searching for effective therapies for certain conditions, the same logic most certainly applies. For example in bone homeostasis, as well as bone destruction from cancer and autoimmune disease, doctors and researchers seem to have a decent understanding as to what to do. These conditions come about largely because of a lack of osteoclasts. Since these osteoclasts are generated largely because of the receptor activator NF-_kB ligand (RANKL), much attention has been paid to the role of RANK and RANKL in the disappearance of osteoclasts. Essentially, the loss or mutation of RANKL leads to this disappearance. Up until this point, no treatment for conditions related to bone loss has been found that does not involve the induction of RANK. But recent studies have called this seemingly sound link into question. Some researchers have found that lysyl oxidase (LOX) promotes bone metastasis through RANKL-independent osteoclastogenesis. Additionally, these studies showed that LOX was able to do this with greater efficiency than RANKL, suggesting this may be a better approach for bone-loss conditions.

However, before researchers go too far, it is important to verify results. Some questions in the methodology of these previous studies have raised some doubts, and this was exactly the nature of the study conducted by Tsukasaki et al. from the University of Tokyo. They performed a series of tests to verify the validity of these claims that LOX could be more effective in osteoclasgenesis than RANKL by eliminating the presence of RANKL and RANK in any form around a cellular environment. To do this, they needed to carefully measure LOX activity, which they did using the Amplite^® Fluorimetric Lysyl Oxidase Assay Kit. This assay kit uses Amplite's proprietary substrate to measure LOX oxidation through the level of hydrogen peroxide released during the oxidation. The oxidation is detected using the substrate in HRP, which allows for the detection of sub ng/ML LOX, making this assay much more sensitive and accurate than other flourometric assays.

The results of this study ended up proving that while LOX has the ability to induce RANKL expression on stromal cells, it fails to substitute for RANKL in oseteoclastogenesis. This contradicts what was found in previous studies. One might look at this as a disappointment because research indicated LOX could be a more effective treatment, however, in science, there is no disappointment in the truth. These results help prevent further research into a less effective treatment, which would waste both time and precious resources. Researchers could not have arrived at these conclusions without the benefit of quality measurement tools such as the Amplite^® Fluorimetric Lysyl Oxidase Assay Kit. Its higher level of sensitivity allows for more accurate results, which boosts the viability of, and confidence for, the finding. Rigorous tests such as these help ensure the greater medical research community keeps marching in the right direction.

References

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1. Tsukasaki, Masayuki, et al. "LOX fails to substitute for RANKL in osteoclastogenesis." Journal of Bone and Mineral Research 32.3 (2017): 434-439.