ECTS Abstracts (2015) 1 P73

The use of bone anabolic factors for improving tendon-bone regeneration

Mei-Lin Tay1, Ashika Chhana1, Bregina Poole1, Brendan Coleman2, Jillian Cornish1 & David Musson1

1University of Auckland, Auckland, New Zealand; 2Counties Manukau District Health Board, Auckland, New Zealand.

Background: Healing of hard-soft tissue interfaces are a significant clinical problem. The tendon-bone interface is a particular problem due to the high levels of strain it is exposed to. Furthermore, there are currently no accepted biological treatments for improving the healing of this complicated tissue interface. Parathyroid hormone (PTH) is an anabolic factor used clinically to enhance bone formation. It increases insulin growth factor-1 expression (a factor important in tendon healing), and has recently been shown to enhance tendon healing in a model of flexor tendon injury, and tendon-bone healing in a model of anterior cruciate ligament reconstruction. Lactoferrin is a pleiotropic growth factor with anabolic effects on bone and cartilage; both important constituents of the tendon-bone interface, where tendons insert into distinct layers of cartilage and finally bone. Here, we aim to elucidate the effects of PTH and lactoferrin on tendon cell biology.

Methods: Primary tenocytes were harvested from rat tails and treated with a range of concentrations of PTH and bovine lactoferrin (bLF). Cell growth was determined using alamarBlue® assays and collagen deposition was measured by Sirius red dye release. Tenocyte differentiation was assessed by measuring gene expression levels using real-time PCR.

Results: Neither PTH nor bLF had an effect on tenocyte growth or collagen production. Similarly, bLF had no effect on the expression on genes important in tendon biology, such as scleraxis and tenomodulin, but did increase the expression of alkaline phosphatase. PTH decreased scleraxis expression, aggrecan and sox9 expression and increased alkaline phosphatase expression.

Conclusion: These results indicate that both PTH and lactoferrin are likely to induce tenocytes to trans-differentiate away from a tendon-specific lineage, suggesting that while they may not be ideal for tendon regeneration, they may have use in the healing of tendon-bone interfaces where tendon inserts into cartilage, and then bone.

Disclosure: The authors declared no competing interests. This research was supported by the Health Research Council of New Zealand (Grant number 12/1110).

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