Higher BMP Expression in Tendon Stem/Progenitor Cells Contributes to the Increased Heterotopic Ossification in Achilles Tendon With Aging

Guangchun Dai; Guangchun Dai; Guangchun Dai; Guangchun Dai; Yingjuan Li; Junyan Liu; Junyan Liu; Junyan Liu; Junyan Liu; Cheng Zhang; Cheng Zhang; Cheng Zhang; Cheng Zhang; Minhao Chen; Minhao Chen; Minhao Chen; Minhao Chen; Panpan Lu; Panpan Lu; Panpan Lu; Panpan Lu; Yunfeng Rui; Yunfeng Rui; Yunfeng Rui; Yunfeng Rui

doi:10.3389/fcell.2020.570605

Frontiers in Cell and Developmental Biology (Sep 2020)

Higher BMP Expression in Tendon Stem/Progenitor Cells Contributes to the Increased Heterotopic Ossification in Achilles Tendon With Aging

Guangchun Dai,
Guangchun Dai,
Guangchun Dai,
Guangchun Dai,
Yingjuan Li,
Junyan Liu,
Junyan Liu,
Junyan Liu,
Junyan Liu,
Cheng Zhang,
Cheng Zhang,
Cheng Zhang,
Cheng Zhang,
Minhao Chen,
Minhao Chen,
Minhao Chen,
Minhao Chen,
Panpan Lu,
Panpan Lu,
Panpan Lu,
Panpan Lu,
Yunfeng Rui,
Yunfeng Rui,
Yunfeng Rui,
Yunfeng Rui

Affiliations

Guangchun Dai: Department of Orthopaedics, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China
Guangchun Dai: School of Medicine, Southeast University, Nanjing, China
Guangchun Dai: Orthopaedic Trauma Institute (OTI), Southeast University, Nanjing, China
Guangchun Dai: Trauma Center, Zhongda Hospital, Southeast University, Nanjing, China
Yingjuan Li: Department of Geriatrics, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China
Junyan Liu: Department of Orthopaedics, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China
Junyan Liu: School of Medicine, Southeast University, Nanjing, China
Junyan Liu: Orthopaedic Trauma Institute (OTI), Southeast University, Nanjing, China
Junyan Liu: Trauma Center, Zhongda Hospital, Southeast University, Nanjing, China
Cheng Zhang: Department of Orthopaedics, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China
Cheng Zhang: School of Medicine, Southeast University, Nanjing, China
Cheng Zhang: Orthopaedic Trauma Institute (OTI), Southeast University, Nanjing, China
Cheng Zhang: Trauma Center, Zhongda Hospital, Southeast University, Nanjing, China
Minhao Chen: Department of Orthopaedics, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China
Minhao Chen: School of Medicine, Southeast University, Nanjing, China
Minhao Chen: Orthopaedic Trauma Institute (OTI), Southeast University, Nanjing, China
Minhao Chen: Trauma Center, Zhongda Hospital, Southeast University, Nanjing, China
Panpan Lu: Department of Orthopaedics, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China
Panpan Lu: School of Medicine, Southeast University, Nanjing, China
Panpan Lu: Orthopaedic Trauma Institute (OTI), Southeast University, Nanjing, China
Panpan Lu: Trauma Center, Zhongda Hospital, Southeast University, Nanjing, China
Yunfeng Rui: Department of Orthopaedics, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China
Yunfeng Rui: Orthopaedic Trauma Institute (OTI), Southeast University, Nanjing, China
Yunfeng Rui: Trauma Center, Zhongda Hospital, Southeast University, Nanjing, China
Yunfeng Rui: China Orthopedic Regenerative Medicine Group, Hangzhou, China

DOI: https://doi.org/10.3389/fcell.2020.570605
Journal volume & issue: Vol. 8

Abstract

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Although the mineralization in tendon tissue has been reported in a series of aging and disease models, the underlying mechanisms remain unknown. This study aimed to describe the appearance of heterotopic ossification in rat Achilles tendon and further verify whether this tissue metaplasia is related to the enhanced osteogenic differentiation of tendon stem/progenitor cells (TSPCs) owing to the higher expression of bone morphogenetic proteins (BMP-2/4/7) with aging. The male SD rats, aged 4, 8, and 20 months (M), were used. The analyses of ossification and BMP expression in tendon were tested by radiological view (X-ray and CT), histological staining [hematoxylin and eosin (HE), Alcian blue, and Alizarin red], immunohistochemistry, and Western blot. The osteogenic differentiation potential and BMP expression of TSPCs were examined by Alizarin red S staining and real-time PCR. TSPCs were treated with BMP-2 or noggin, and the osteogenic differentiation potential was also examined. X-ray and CT showed the appearance of heterotopic ossification in tendon, and the volume and density of ossification was increased with aging. Histological staining showed the appearance of calcified region surrounded by chondrocyte-like cells and the increased osteogenesis-related gene and BMP expression in ossified tendon with aging. Moreover, the osteogenic differentiation potential and BMP expression in TSPCs isolated from ossified tendon were increased with aging. Additionally, BMP-2 increased the calcium nodule formation and osteogenesis-related gene expression in TSPCs. The addition of noggin inhibited BMP-induced enhancement of osteogenic differentiation. Thus, these findings suggested that the enhanced osteogenic differentiation of TSPCs contributes to the increased heterotopic ossification in aged tendon, which might be induced by the higher expression of BMPs with aging.

Published in Frontiers in Cell and Developmental Biology

ISSN: 2296-634X (Online)
Publisher: Frontiers Media S.A.
Country of publisher: Switzerland
LCC subjects: Science: Biology (General)
Website: https://www.frontiersin.org/journals/cell-and-developmental-biology

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