Open Access

The role of inhibition by phosphocitrate and its analogue in chondrocyte differentiation and subchondral bone advance in Hartley guinea pigs

  • Authors:
    • Yubo Sun
    • Alex J. Kiraly
    • Michael Cox
    • David R. Mauerhan
    • Edward N. Hanley
  • View Affiliations

  • Published online on: February 7, 2018     https://doi.org/10.3892/etm.2018.5846
  • Pages: 3320-3328
  • Copyright: © Sun et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Phosphocitrate (PC) and its analogue, PC‑β ethyl ester, inhibit articular cartilage degeneration in Hartley guinea pigs. However, the underlying molecular mechanisms remain unclear. The present study aimed to investigate the hypothesis that PC exerted its disease‑modifying effect on osteoarthritis (OA), in part, by inhibiting a molecular program similar to that in the endochondral pathway of ossification. The results demonstrated that severe proteoglycan loss occurred in the superficial and middle zones, as well as in the calcified zone of articular cartilage in the Hartley guinea pigs. Subchondral bone advance was greater in the control Hartley guinea pigs compared with PC‑ or PC analogue‑treated guinea pigs. Resorption of cartilage bars or islands and vascular invasion in the growth plate were also greater in the control guinea pigs compared with the PC‑ or PC analogue‑treated guinea pigs. The levels of matrix metalloproteinase‑13 and type X collagen within the articular cartilage and growth plate were significantly increased in the control guinea pigs compared with PC‑treated guinea pigs (P<0.05). These results indicated that articular chondrocytes in Hartley guinea pigs exhibited a hypertrophic phenotype and recapitulated a developmental molecular program similar to the endochondral pathway of ossification. Activation of this molecular program resulted in resorption of calcified articular cartilage and subchondral bone advance. This suggests that PC and PC analogues exerted their OA disease‑modifying activity, in part, by inhibiting this molecular program.
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April-2018
Volume 15 Issue 4

Print ISSN: 1792-0981
Online ISSN:1792-1015

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Spandidos Publications style
Sun Y, Kiraly AJ, Cox M, Mauerhan DR and Hanley EN: The role of inhibition by phosphocitrate and its analogue in chondrocyte differentiation and subchondral bone advance in Hartley guinea pigs. Exp Ther Med 15: 3320-3328, 2018.
APA
Sun, Y., Kiraly, A.J., Cox, M., Mauerhan, D.R., & Hanley, E.N. (2018). The role of inhibition by phosphocitrate and its analogue in chondrocyte differentiation and subchondral bone advance in Hartley guinea pigs. Experimental and Therapeutic Medicine, 15, 3320-3328. https://doi.org/10.3892/etm.2018.5846
MLA
Sun, Y., Kiraly, A. J., Cox, M., Mauerhan, D. R., Hanley, E. N."The role of inhibition by phosphocitrate and its analogue in chondrocyte differentiation and subchondral bone advance in Hartley guinea pigs". Experimental and Therapeutic Medicine 15.4 (2018): 3320-3328.
Chicago
Sun, Y., Kiraly, A. J., Cox, M., Mauerhan, D. R., Hanley, E. N."The role of inhibition by phosphocitrate and its analogue in chondrocyte differentiation and subchondral bone advance in Hartley guinea pigs". Experimental and Therapeutic Medicine 15, no. 4 (2018): 3320-3328. https://doi.org/10.3892/etm.2018.5846