The combined use of kartogenin and platelet-rich plasma promotes fibrocartilage formation in the wounded rat Achilles tendon entheses

J Zhang; T Yuan; N Zheng; Y Zhou; M V Hogan; J H-C Wang

doi:10.1302/2046-3758.64.BJR-2017-0268.R1

The combined use of kartogenin and platelet-rich plasma promotes fibrocartilage formation in the wounded rat Achilles tendon entheses

Bone Joint Res. 2017 Apr;6(4):231-244. doi: 10.1302/2046-3758.64.BJR-2017-0268.R1.

Authors

J Zhang¹, T Yuan¹, N Zheng², Y Zhou¹, M V Hogan¹, J H-C Wang³

Affiliations

¹ Department of Orthopaedic Surgery, University of Pittsburgh School of Medicine, 200 Lothrop Street, Pittsburgh, Pennsylvania 15213, USA.
² Department of Mechanical Engineering, University of North Carolina, 9201 University City Blvd, Mechanical Engineering, Duke 201, Charlotte, North Carolina, USA.
³ Department of Orthopaedic Surgery, University of Pittsburgh School of Medicine, 200 Lothrop Street, Pittsburgh, Pennsylvania 15213, USA wanghc@pitt.edu.

PMID: 28450316
PMCID: PMC5415905
DOI: 10.1302/2046-3758.64.BJR-2017-0268.R1

Abstract

Objectives: After an injury, the biological reattachment of tendon to bone is a challenge because healing takes place between a soft (tendon) and a hard (bone) tissue. Even after healing, the transition zone in the enthesis is not completely regenerated, making it susceptible to re-injury. In this study, we aimed to regenerate Achilles tendon entheses (ATEs) in wounded rats using a combination of kartogenin (KGN) and platelet-rich plasma (PRP).

Methods: Wounds created in rat ATEs were given three different treatments: kartogenin platelet-rich plasma (KGN-PRP); PRP; or saline (control), followed by histological and immunochemical analyses, and mechanical testing of the rat ATEs after three months of healing.

Results: Histological analysis showed well organised arrangement of collagen fibres and proteoglycan formation in the wounded ATEs in the KGN-PRP group. Furthermore, immunohistochemical analysis revealed fibrocartilage formation in the KGN-PRP-treated ATEs, evidenced by the presence of both collagen I and II in the healed ATE. Larger positively stained collagen III areas were found in both PRP and saline groups than those in the KGN-PRP group. Chondrocyte-related genes, SOX9 and collagen II, and tenocyte-related genes, collagen I and scleraxis (SCX), were also upregulated by KGN-PRP. Moreover, mechanical testing results showed higher ultimate tensile strength in the KGN-PRP group than in the saline control group. In contrast, PRP treatment appeared to have healed the injured ATE but induced no apparent formation of fibrocartilage. The saline-treated group showed poor healing without fibrocartilage tissue formation in the ATEs.

Conclusions: Our results show that injection of KGN-PRP induces fibrocartilage formation in the wounded rat ATEs. Hence, KGN-PRP may be a clinically relevant, biological approach to regenerate injured enthesis effectively.Cite this article: J. Zhang, T. Yuan, N. Zheng, Y. Zhou, M. V. Hogan, J. H-C. Wang. The combined use of kartogenin and platelet-rich plasma promotes fibrocartilage formation in the wounded rat Achilles tendon entheses. Bone Joint Res 2017;6:231-244. DOI: 10.1302/2046-3758.64.BJR-2017-0268.R1.

Keywords: Enthesis; fibrocartilage; kartogenin; platelet-rich plasma; tendon-bone junction.