In vitro collagen biomarkers in mechanically stimulated human tendon cells: a systematic review

ABSTRACT

Objective

The aim of this study was to comprehensively examine and summarize the available in vitro evidence regarding the relationship between mechanical stimulation and biomarkers of collagen synthesis in human-derived tendon cells.

Methods

Systematic review with narrative analyses and risk of bias assessment guided by the Health Assessment and Translation tool. The electronic databases MEDLINE (Ovid), EMBASE (Ovid), CENTRAL (Ovid) and COMPENDEX (Engineering Village) were systematically searched from inception to 3 August 2023. Inclusion criteria encompassed English language, original experimental, or quasi-experimental in vitro publications that subjected human tendon cells to mechanical stimulation, with collagen synthesis (total collagen, type I, III, V, XI, XII, and XIV) and related biomarkers (matrix metalloproteinases, transforming growth factor β, scleraxis, basic fibroblast growth factor) as outcomes.

Results

Twenty-one publications were included. A pervasive definite high risk of bias was evident in all included studies. Owing to incomplete outcome reporting and heterogeneity in mechanical stimulation protocols, planned meta-analyses were unfeasible. Reviewed data suggested that human tendon cells respond to mechanical stimulation with increased synthesis of collagen (e.g., COL1A1, procollagen, total soluble collagen, etc.), scleraxis and several matrix metalloproteinases. Results also indicate that mechanical stimulation dose magnitude may influence synthesis in several biomarkers.

Conclusions

A limited number of studies, unfortunately characterized by a definite high risk of bias, suggest that in vitro mechanical stimulation primarily increases type I collagen synthesis by human tendon cells. Findings from this systematic review provide researchers and clinicians with biological evidence concerning the possible beneficial influence of exercise and loading on cellular-level tendon adaptation.

KEYWORDS:

• Tendon cell
• collagen synthesis
• cell stimulation
• tendon adaptation
• cyclic loading

Acknowledgments

We thank Dr Chris Napier for discussions which led to the formulation of this study idea.

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. As previously mentioned, two authors had affiliations with publications included in the current review, and we accounted for this competing interest by isolating the authors from RoB scoring by bringing in a third-party reviewer.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Authors’ contributions

CB, KS, and AS designed the data collection procedures and search strategies. KS and AS carried out data collection. KS and FD performed risk of bias assessment. KS, AS, RM, MH, and FD drafted the article. All authors approved the final article.

Additional information

Funding

The author(s) reported that there is no funding associated with the work featured in this article.