NAMPT-Improved Mitochondrial Function Alleviates Degenerative Rotator Cuff Tendinopathy in Aged Mice

Yao Zhang; Shuai Lu; Gang Yu; Chongyang Wang; Qichun Zhao

doi:10.2106/JBJS.22.00894

NAMPT-Improved Mitochondrial Function Alleviates Degenerative Rotator Cuff Tendinopathy in Aged Mice

J Bone Joint Surg Am. 2023 Oct 4;105(19):1502-1511. doi: 10.2106/JBJS.22.00894. Epub 2023 Aug 24.

Authors

Yao Zhang¹, Shuai Lu², Gang Yu¹, Chongyang Wang³, Qichun Zhao^{1

2}

Affiliations

¹ Department of Orthopedics, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, People's Republic of China.
² Department of Orthopedics, Affiliated Provincial Hospital of Anhui Medical University, Hefei, People's Republic of China.
³ Department of Orthopedics, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.

PMID: 37616388
DOI: 10.2106/JBJS.22.00894

Abstract

Background: Age-related rotator cuff tendinopathy (RCT) is associated with increased rotator cuff tear and postoperative retear rates. This study aimed to determine whether nicotinamide phosphoribosyltransferase (NAMPT) can alleviate degenerative RCT and prevent postoperative retears by reversing mitochondrial dysfunction in aged mice.

Methods: We assigned 32 young (4 months) and 64 aged (19 to 20 months) male wild-type C57BL/6 mice to young, aged, and aged NAMPT-treated (ANAMPT) groups (n = 32 each). Mice in the ANAMPT group underwent subacromial injection with NAMPT-loaded fibrin gel, whereas the other 2 groups were injected with fibrin gel alone. Histological staining and each of the biomechanical and mitochondrial function tests were performed using 8 samples each.

Results: Histological staining in the aged group revealed decreased cellularity, disrupted fiber architecture, and reduced type-I collagen content inside tendon tissues proximal to the enthesis, demonstrating the spontaneous development of age-related degenerative RCT. Compared with the young group, the maximum tendon-to-bone failure load (4.22 ± 0.81 versus 5.52 ± 0.81 N, p = 0.0106) and maximum suture cut-through force (0.83 ± 0.08 versus 1.07 ± 0.10 N, p = 0.0006) of degenerated tendon tissues in the aged group were significantly lower. Significantly reduced nicotinamide adenine dinucleotide (NAD + ) levels, adenosine triphosphate (ATP) production, and citrate synthase activity indicated that mitochondrial dysfunction was closely related to the development of the degenerative RCT. Furthermore, NAMPT-improved mitochondrial function alleviated age-induced degenerative histological changes and increased the maximum failure load (5.32 ± 0.68 N, p = 0.0375) and maximum suture cut-through force (0.99 ± 0.13 N, p = 0.0285).

Conclusions: Spontaneously developed degenerative RCT in aged mice mimicked the clinical situation in elderly patients. NAMPT-improved mitochondrial function could alleviate age-induced degenerative RCT and prevent postoperative suture cut-through of tendons with degenerative RCT.

Clinical relevance: This study confirmed the spontaneous development of degenerative RCT in aged mice, which will facilitate future studies of this condition. The results also suggest that NAMPT offers a novel therapeutic approach for treating age-related degenerative RCT.