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. 2017 Sep 18;7(2):215-222.
doi: 10.11138/mltj/2017.7.2.215. eCollection 2017 Apr-Jun.

Lactoferrin and parathyroid hormone are not harmful to primary tenocytes in vitro, but PDGF may be

David S Musson  1 , Mei Lin Tay  1 , Ashika Chhana  1 , Bregina Pool  1 , Brendan Coleman  2 , Dorit Naot  1 , Jillian Cornish  1
Affiliations

Lactoferrin and parathyroid hormone are not harmful to primary tenocytes in vitro, but PDGF may be

David S Musson et al. Muscles Ligaments Tendons J. .

Abstract

Introduction: Recently, bone-active factors such as parathyroid hormone and lactoferrin, have been used in pre-clinical models to promote tendon healing. How-ever, there is limited understanding of how these boneactive factors may affect the cells of the ten-don themselves. Here, we present an in vitro study assessing the effects of parathyroid hor-mone and lactoferrin on primary tendon cells (tenocytes), and compare their responses to the tenogenic factors, PDGF, IGF-1 and TGF-β.

Materials and methods: Tenocyte proliferation and collagen production were assessed by alamarBlue® and Sirius red as-says, respectively. To assess tenocyte trans-differentiation, changes in the expression of genes important in tenocyte, chondrocyte and osteoblast biology were determined using real-time PCR.

Results: Parathyroid hormone and lactoferrin had no effect on tenocyte growth or collagen production, with minimal changes in gene expression and no detrimental effects observed to suggest trans-differentiation away from tendon cell behaviour. Tenogenic factors PDGF, IGF-1 and TGF all increasetenocyte collagen production, however, the gene expression data suggests that PDGF promotes severe de-differentiation of the tenocytes.

Discussion: Our findings suggest that using parathyroid hormone or lactoferrin as a singular factor to promote tendon healing may not be of benefit, but for use in tendon-bone healing there would be no detrimental effect on the tendon itself.

Keywords: growth factors; healing; lactoferrin; parathyroid hormone; tendon.

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Conflict of interest statement

Conflicts of Interest The Authors declare that there is no conflict of interest.

Figures

Figure 1
Figure 1
PDGF increases tenocyte cell growth. Effects of the bone active factors lactoferrin and PTH (1-34), and the tenogenic factors PDGF, TGF-β and IGF-1 on primary rat tenocyte cell growth, determined by alamarBlue® assay. Data are presented as mean ratio of control ± SEM. n ≥ 4. *=significantly different from control (P < 0.05).
Figure 2
Figure 2
Tenocyte growth factors increase primary rat tenocyte collagen deposition. Effects of the bone active factors lactoferrin and PTH (1-34), and the tenogenic factors PDGF, TGF-β and IGF-1 on primary rat tenocyte collagen production, determined by sirius red assay. Data are presented as mean ratio of control ± SEM. n =3. *=significantly different from control (P < 0.05).
Figure 3
Figure 3
Lactoferrin had little effect on tenocyte gene expression. Effects of increasing concentrations of lactoferrin on the expression of tendon and non-tendon related genes in primary rat tenocytes. Data are presented as means ± SEM. n=3. *=significantly different from control (P < 0.05).
Figure 4
Figure 4
PTH (1-34 ) increased gene expression associated with matrix assembly and decreased chondrocyte marker expression. Effects of increasing concentrations of PTH (1-34) on the expression of tendon and non-tendon related genes in primary rat tenocytes. Data are presented as means ± SEM. n=3. *=significantly different from control (P < 0.05).
Figure 5
Figure 5
PDGF caused a de-differentiation of tenocytes. Effects of increasing concentrations of PDGF on the expression of tendon and non-tendon related genes in primary rat tenocytes. Data are presented as means ± SEM. n=3. *=significantly different from control (P < 0.05).
Figure 6
Figure 6
TGF-β enhanced tenomodullin expression and decreases osteoblastic marker gene expression. Effects of increasing concentrations of TGF-β on the expression of tendon and non-tendon related genes in primary rat tenocytes. Data are presented as means ± SEM. n=3. *=significantly different from control (P < 0.05).
Figure 7
Figure 7
IGF enhanced tenomodullin expression in tenocytes, as well as non-tenoytic gene markers. Effects of increasing concentrations of IGF-1 on the expression of tendon and non-tendon related genes in primary rat tenocytes. Data are presented as means ± SEM. n=3. *=significantly different from control (P < 0.05).
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