Sirtuin 6 Overexpression Improves Rotator Cuff Tendon-to-Bone Healing in the Aged
Young Jae Moon,
Baoning Cui,
Se-Young Cho,
Jae Won Hwang,
Hee-Chung Chung,
Joseph Kwon,
Duwoon Kim,
Kyu Yun Jang,
Jung Ryul Kim,
Sung Il Wang
Affiliations
Young Jae Moon
Department of Biochemistry and Orthopaedic Surgery, Research Institute of Clinical Medicine of Jeonbuk National University-Biomedical Research Institute of Jeonbuk National University Hospital, Jeonbuk National University Medical School, Jeonju 54896, Republic of Korea
Baoning Cui
Department of Orthopaedic Surgery, Research Institute of Clinical Medicine of Jeonbuk National University-Biomedical Research Institute of Jeonbuk National University Hospital, Jeonbuk National University Medical School, Jeonju 54896, Republic of Korea
Se-Young Cho
Department of Food Science and Technology, Foodborne Virus Research Center, Chonnam National University, Gwangju 61186, Republic of Korea
Jae Won Hwang
Department of Orthopaedic Surgery, Research Institute of Clinical Medicine of Jeonbuk National University-Biomedical Research Institute of Jeonbuk National University Hospital, Jeonbuk National University Medical School, Jeonju 54896, Republic of Korea
Hee-Chung Chung
Department of BioChemical Analysis, Korea Basic Science Institute, Daejeon 30147, Republic of Korea
Joseph Kwon
Department of BioChemical Analysis, Korea Basic Science Institute, Daejeon 30147, Republic of Korea
Duwoon Kim
Department of Food Science and Technology, Foodborne Virus Research Center, Chonnam National University, Gwangju 61186, Republic of Korea
Kyu Yun Jang
Department of Pathology, Jeonbuk National University Medical School, Jeonju 54896, Republic of Korea
Jung Ryul Kim
Department of Orthopaedic Surgery, Research Institute of Clinical Medicine of Jeonbuk National University-Biomedical Research Institute of Jeonbuk National University Hospital, Jeonbuk National University Medical School, Jeonju 54896, Republic of Korea
Sung Il Wang
Department of Orthopaedic Surgery, Research Institute of Clinical Medicine of Jeonbuk National University-Biomedical Research Institute of Jeonbuk National University Hospital, Jeonbuk National University Medical School, Jeonju 54896, Republic of Korea
Aging is an independent risk factor for recurrent tearing after surgical repair of rotator cuff ruptures around the tendon-to-bone area. However, aging signature factors and related mechanisms involved in the healing of the rotator cuff are still unknown. We hypothesized that differences in proteins involved in the rotator cuff according to age may affect tendon-to-bone healing. The proteome analysis performed to identify the signature aging proteins of the rotator cuff confirmed the sirtuin signal as an age-specific protein. In particular, the expression of SIRT6 was markedly down-regulated with age. Ingenuity pathway analysis of omics data from age-dependent rat rotator cuffs and linear regression from human rotator cuffs showed SIRT6 to be closely related to the Wnt/β-catenin signal. We confirmed that overexpression of SIRT6 in the rotator cuff and primary tenocyte regulated canonical Wnt signaling by inhibiting the transcriptional expression of sclerostin, a Wnt antagonist. Finally, SIRT6 overexpression promoted tendon-to-bone healing after tenotomy with reconstruction in elderly rats. This approach is considered an effective treatment method for recovery from recurrent rotator cuff tears, which frequently occur in the elderly.
