The Effect of Age on Bone and Its Response to Mechanical Stimulation

Bone is a specialized connective tissue system which is able to regulate its own bone mass and architecture to meet the daily demands of its external environment. Mechanical loading directly or indirectly influences the activity of cell populations to deposit, maintain, or remove bone tissue as appropriate, which is integral to skeletal adaptation to load. With advancing age there are alterations in bone structure and mineralization which are often associated with an increase in osteoporotic fracture risk. The transduction of mechanical cues affects bone structure and mineralization and could be altered with advancing age. Current in vivo and in vitro data suggest age may affect the capacity of bone cells to respond to mechanical stimulation; however the effect of age on this response to mechanical stimulation in the regenerative skeleton and on osteocytes, which are thought to be the primary mechanical sensors, is unknown.

It was hypothesized that the influence of mechanical factors on the maintenance or repair of bone is influenced by age. In this study regenerative specimens primarily composed of osteocytes were produced in young and old animals. Their response to mechanical loading via nitric oxide (NO), prostaglandin E2 (PGE2), connexin 43 (Cx43), MAP Kinase, and c-fos signaling was assessed via ELISA and western blot and compared to the response of age matched mature bone. Regenerative specimens from young animals had a higher net increase in NO, PGE2, Cx43 and c-fos after mechanical stimulation than regenerative specimens from old animals. The mechanical stimulation of regenerative tissue resulted in a higher net increase of mechanical response molecules than mature bone in both age groups. This was observed at an earlier time point of regeneration in specimens produced in young animals which could initiate earlier remodeling and thus maintaof regenerative tissue resulted in a higher net increase of mechanical response molecules than mature bone in both age groups. This was observed at an earlier time point of regeneration in specimens produced in young animals which could initiate earlier remodeling and thus maintain a mean tissue age that is fairly constant and less susceptible to brittle fracture. Progenitor cells from old animals exhibited delayed mineralization and a decrease response to mechanical stimulation throughout differentiation. The data from this study suggests primary cells from old donors with appropriate differentiation time and mechanical stimulus may promote bone formation, which could make them useful for tissue engineering applications. In addition, key differences in mechanical response were highlighted which have the potential for further investigation to develop therapeutics for bone loss in aging populations. in a mean tissue age that is fairly constant and less susceptible to brittle fracture.

Progenitor cells from old animals exhibited delayed mineralization and a decrease response to mechanical stimulation throughout differentiation. The data from this study suggests primary cells from old donors with appropriate differentiation time and mechanical stimulus may promote bone formation, which could make them useful for tissue engineering applications. In addition, key differences in mechanical response were highlighted which have the potential for further investigation to develop therapeutics for bone loss in aging populations.

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Year

Entry

1983

Bonar LC, Roufosse AH, Sabine WK, Grynpas MD, Glimcher MJ. X-ray diffraction studies of the crystallinity of bone mineral in newly synthesized and density fractionated bone. Calcif Tiss Int. December 1983;35(2):202-209.

2003

Simmons CA, Matlis S, Thornton AJ, Chen S, Wang C-Y, Mooney DJ. Cyclic strain enhances matrix mineralization by adult human mesenchymal stem cells via the extracellular signal-regulated kinase (ERK1/2) signaling pathway. J Biomech. August 2003;36(8):1087-1096.

2006

Sawakami K, Robling AG, Ai M, Pitner ND, Liu D, Warden SJ, Li J, Maye P, Rowe DW, Duncan RL, Warman ML, Turner CH. The Wnt co-receptor LRP5 is essential for skeletal mechanotransduction but not for the anabolic bone response to parathyroid hormone treatment. J Biol Chem. August 18, 2006;281(33):23698-23711.

2006

Rubin J, Rubin C, Jacobs CR. Molecular pathways mediating mechanical signaling in bone. Gene. February 15, 2006;367:1-16.

1987

Frost HM. The mechanostat: a proposed pathogenic mechanism of osteoporoses and the bone mass effects of mechanical and nonmechanical agents. Bone Miner. April 1987;2(2):73-85.