Parathyroid hormone 1–34 enhances extracellular matrix deposition and organization during flexor tendon repair

Lee, Dong Hoon; Southgate, Richard D.; Farhat, Youssef M.; Loiselle, Alayna E.; Hammert, Warren C.; Awad, Hani A.; O’Keefe, Regis J.

doi:10.1002/jor.22735

Cited by 23 publications

(19 citation statements)

References 26 publications

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“…PTH (40 mg/kg) was therefore administered, by either subcutaneous or intraperitoneal injections. In comparison to controls, PTH promoted an early formation of reparative tissue associated with an increased expression of extracellular matrix genes, including fibrillar collagens, type I and type III, and fibronectin 47 . Similarly to previous experiments, no significant differences in tensile strength were seen.…”

Section: Therapeutic Perspectivesmentioning

confidence: 99%

Therapeutic use of hormones on tendinopathies: a narrative review

Abate

Guelfi

Pantalone

et al. 2016

MLTJ

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SummaryBackground: Hormones can modify tendon homeostasis, some of them leading to tendon damage, while others are essentials for healing. This narrative review summarizes the current knowledge on the topic, focusing on the hormones normally secreted by endocrine glands. Methods: A search in PubMed, Web of Knowledge and EMBASE, using the terms tendinopathy or tendon, combined with estrogens, testosterone, thyroid and parathyroid hormones, glucocorticoids and growth hormone, independently, was performed. Relevant articles focusing on the correlation between hormones and tendons, and their therapeutic use in tendinopathies, were selected. Results: Tendon abnormalities observed in subjects with hyperparathyroidism, hypercortisolism and acromegaly are described. At present, experimental studies and preliminary observations in humans suggest that parathyroid and growth hormones, locally administered, are promising therapeutic tools in specific tendon disorders. Local injections of glucocorticoids are useful in several tendinopathies, exploiting their anti-inflammatory and anti-proliferative properties, but carry the risk of further tendon degeneration and ruptures, due

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Section: Therapeutic Perspectivesmentioning

confidence: 99%

Therapeutic use of hormones on tendinopathies: a narrative review

Abate

Guelfi

Pantalone

et al. 2016

MLTJ

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“…This model has been used to assess knock-out mouse models 13,14 , and to test different pharmacological approaches to improve healing 15–18 . Histological analyses of this model, using immunohistochemistry and in situ hybridization, can provide important insights in to the localization of key genes and proteins during healing.…”

Section: Introductionmentioning

confidence: 99%

Murine Flexor Tendon Injury and Repair Surgery

Ackerman

Loiselle

2016

JoVE

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Tendon connects muscle and bone, facilitating movement of nearly the entire body. In the hand, flexor tendons enable flexion of the fingers and general hand function. Injuries to the flexor tendons are common, and satisfactory healing is impaired due to excess scar tissue and adhesions between the tendon and surrounding tissue. However, very little is known about the molecular and cellular components of flexor tendon repair. To that end, we have previously described a murine model of flexor tendon repair that recapitulates many aspects of healing in humans including impaired range of motion and decreased mechanical properties. Here we provide an in-depth description and demonstration of this surgical procedure to completely transect and repair the flexor digitorum longus (FDL) tendon in the hind paw of the mouse. This technique can be used to conduct lineage analysis of different cell types, assess the effects of gene gain or loss-of-function, and to test the efficacy of pharmacological interventions in the healing process. However, there are two primary limitations to this model: i) the FDL tendon in the mid-portion of the murine hind paw, where the transection and repair occur, is not surrounded by a synovial sheath. Therefore this model does not account for the potential contribution of the sheath the scar formation process. ii) To protect the integrity of the repair site, the tendon is release at the myotendinous junction, decreasing the mechanical forces of the tendon, likely contributing to increased scar formation. In addition, we demonstrate the use of the cytospin method to identify and quantify different cell populations during healing. Isolation of sufficient cells during the healing process for flow cytometric analysis has proved quite challenging; cytospin requires far fewer cells but allows for simple immunofluorescent labeling and quantification of cells or proteins of interest.

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“…Interestingly, PTH treatment reduced the expression of the chondrocytic genes aggrecan and sox9, suggesting that it may also help in the maintenance of a tenocytic lineage. The clinical correlation between high serum PTH and poor tendon health is likely due to continuous exposure to PTH and increased bone resorbing osteoclast activity at the tendon-bone interface 14,15 , rather than the short or intermittent administration discussed in this paper and the pre-clinical studies published to date [7][8][9] . These results suggest that PTH may have a slight beneficial effect on tendon healing, particularly in the tendon-bone area as pre-clinical studies have suggested.…”

Section: Discussionmentioning

confidence: 89%

“…However, when taken into context with previously published data, it may have a use in treating tendonbone defects, where tendon, fibrocartilage and bone occur within millimetres. Clinically, hypothyroidism has been linked to musculoskeletal problems in humans 12 , and increased serum PTH is associated with tendon laxity and spontaneous tendon rupture [13][14][15] , although pre-clinical in vivo studies using PTH suggest it may have some benefit in tendon healing [7][8][9] . In our study PTH had no effect on tendon proliferation or collagen production, but did increase the expression of decorin, which plays a role in matrix assembly and could have direct implications on collagen fibrillogenesis.…”

Section: Discussionmentioning

confidence: 99%

“…Recently there has been a number of small animal studies looking at the use of bone-active factors to improve tendon healing, either in models of flexor tendon injury, or in the more complex tendon-bone defects. Parathyroid hormone (PTH) treatment was shown to increase the expression of key matrix genes in the flexor tendon, but had poor effect on joint mobility 7 , while in both ACL reconstruction and rotator cuff healing, PTH increased the amount of bone present at the tendon-bone interface, and therefore increased total pull-out strength of the repaired defect 8,9 . Peptides derived from lactoferrin, a potent bone anabolic factor, have also been shown to improve the healing outcomes of flexor tendons, by reducing focal adhesions 10,11 .…”

Section: Introductionmentioning

confidence: 99%

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

Musson

Tay

Chhana

et al. 2017

MLTJ

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SummaryIntroduction: 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.

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Parathyroid hormone 1–34 enhances extracellular matrix deposition and organization during flexor tendon repair

Cited by 23 publications

References 26 publications

Therapeutic use of hormones on tendinopathies: a narrative review

Therapeutic use of hormones on tendinopathies: a narrative review

Murine Flexor Tendon Injury and Repair Surgery

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

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