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. 2023 Jun 2;16(6):832.
doi: 10.3390/ph16060832.

Beneficial Effects of Zoledronic Acid on Tendons of the Osteogenesis Imperfecta Mouse (Oim)

Antoine Chretien  1 , Guillaume Mabilleau  2   3 , Jean Lebacq  4 , Pierre-Louis Docquier  5 , Catherine Behets  1
Affiliations

Beneficial Effects of Zoledronic Acid on Tendons of the Osteogenesis Imperfecta Mouse (Oim)

Antoine Chretien et al. Pharmaceuticals (Basel). .

Abstract

Osteogenesis imperfecta (OI) is a genetic disorder of connective tissue characterized by spontaneous fractures, bone deformities, impaired growth and posture, as well as extra-skeletal manifestations. Recent studies have underlined an impairment of the osteotendinous complex in mice models of OI. The first objective of the present work was to further investigate the properties of tendons in the osteogenesis imperfecta mouse (oim), a model characterized by a mutation in the COL1A2 gene. The second objective was to identify the possible beneficial effects of zoledronic acid on tendons. Oim received a single intravenous injection of zoledronic acid (ZA group) at 5 weeks and were euthanized at 14 weeks. Their tendons were compared with those of untreated oim (oim group) and control mice (WT group) by histology, mechanical tests, western blotting and Raman spectroscopy. The ulnar epiphysis had a significantly lower relative bone surface (BV/TV) in oim than WT mice. The tendon of the triceps brachii was also significantly less birefringent and displayed numerous chondrocytes aligned along the fibers. ZA mice showed an increase in BV/TV of the ulnar epiphysis and in tendon birefringence. The tendon of the flexor digitorum longus was significantly less viscous in oim than WT mice; in ZA-treated mice, there was an improvement of viscoelastic properties, especially in the toe region of stress-strain curve, which corresponds to collagen crimp. The tendons of both oim and ZA groups did not show any significant change in the expression of decorin or tenomodulin. Finally, Raman spectroscopy highlighted differences in material properties between ZA and WT tendons. There was also a significant increase in the rate of hydroxyproline in the tendons of ZA mice compared with oim ones. This study highlighted changes in matrix organization and an alteration of mechanical properties in oim tendons; zoledronic acid treatment had beneficial effects on these parameters. In the future, it will be interesting to better understand the underlying mechanisms which are possibly linked to a greater solicitation of the musculoskeletal system.

Keywords: bone–tendon unit; oim; osteogenesis imperfecta; tendon; zoledronic acid.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
(A) Sagittal section through the ulnar epiphysis, sirius red staining; the scale bar is 200 µm. (B) Lower limb imaging with in vivo CT in a 14-week-old oim; the arrow shows calcaneus avulsion and tendon calcification. (C) Sagittal section through the triceps surae tendon, toluidin blue staining; the arrows show the calcification front. (D) Sagittal section through triceps brachii tendon in an oim, hematoxylin eosin staining; the arrow shows the successively aligned chondrocytes. (E) Comparison of linear regressions between cross-section area of flexor digitorum superficialis tendons (FDS) and ulna length. R2 = 0.25 for oim, R2 = 0.28 for ZA, R2 = 0.46 for WT; slope: p = 0.14, y-int: p < 0.001. (F) Sagittal section through triceps brachii tendon, polarized light.
Figure 2
Figure 2
(A) Stress strain curve of tensile test of left flexor digitorum longus (FDL) tendons; the deformation was 10% of initial length. (B) Evolution of stress relaxation during the maintenance of deformation of right FDL tendons for 20 s, n = 8 for oim and n = 7 for WT and ZA mice; data are means for each group.
Figure 3
Figure 3
Expression of decorin and tenomodulin in the tail tendon; n = 8 for all groups. Results are expressed as mean ± SEM and normalized to beta-actin. The measurements were made on the same gels but the image is cut off since the third column was an ultimately unexploited group.
See this image and copyright information in PMC

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