The Role of the Bone Proteome in Osteoporosis

There are many known systemic factors which contribute to the pathogenesis of osteoporosis and its treatment. On a basic level, bone frailty results from factors affecting bone reabsorption and formation.

Estrogen deficiency, vitamin deficiencies, receptor activators, growth factors, cytokines, and prostaglandins have all been implicated in osteoporosis at the systemic level.¹ However, the pathophysiology of osteoporosis at the bone level remains unknown.

A recent finding may significantly improve our understanding of the changes that are taking place within the bone and its proteome.

Chaput et al.² compared the femoral necks of osteopenic and an aged matched control group. Using LC-MS/MS, they were able to gain a clear view of the bone proteome, revealing two proteins (carbonic anhydrase I and phosphoglycerate kinase 1) that decreased and one that increased (apolipoprotein A-I) in osteopenic femurs.

This work comes after an earlier piece of work (Alves et al.³) to set up a library of the bone proteome as a source for bone formation modulators and biomarkers for bone diseases. The work of Chaput et al. provides insight into the bone proteome and its intrinsic modulators of bone frailty.

The importance of our understanding of the bone proteome and its involvement in the underlying pathophysiology of osteoporosis should not be underestimated. Current treatments for osteoporosis include nitrogen-containing bisphosphonates (N-BPs). Although the effects of N-BPs on osteoclasts are well defined, their effects on other cell types within bone tissue, including how N-BPs alter the gene expression pattern of osteocytes, are not known. We have an incomplete picture of the bone, and there is an increasing level of research that supports the notion that bisphosphonates have a wide spectrum of targets.⁴ Using proteomics technology has brought us a long way in our understanding of the make-up of our bones. And it has the potential to unlock our understanding of osteoporosis and significantly improve treatment, using more targeted therapeutics.

References

1. Raisz, L.G. (2005) ‘Pathogenesis of osteoporosis: Concepts, conflicts, and prospects‘, The Journal of Clinical Investigation, 115 (12), (pp. 3318-3325)

2. Chaput, C.D., et al. (2012) ‘A proteomic study of protein variation between osteopenic and age-matched control bone tissue‘, Experimental Biology and Medicine, 237 (5), (pp. 491-498)

3. Alves, R.D., et al. (2011) ‘Unraveling the human bone microenvironment beyond the classical extracellular matrix proteins: a human bone protein library‘, Journal of Proteome Research, 10 (10), (pp. 4725-4733)

4. Bivi , N., et al. (2011) ‘Shotgun proteomics analysis reveals new unsuspected molecular effectors of nitrogen-containing bisphosphonates in osteocytes‘, Journal of Proteomics , 74 (7), (pp. 1113-1122)

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