Metabolic Regulation of Tendon Inflammation and Healing Following Injury

Ackerman, Jessica E.; Best, Katherine T.; Muscat, Samantha; Loiselle, Alayna E.

doi:10.1007/s11926-021-00981-4

Cited by 28 publications

(30 citation statements)

References 94 publications

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“…These time points were chosen to cover stages of healing including inflammation, proliferation, and early remodeling. Additionally, previous studies identified alterations in protein expression and tendon mechanical properties as early as 4 weeks postsurgery 5,6,17 . All animals were used for at least two assays (two shoulders from a single animal were never assigned to the same assay).…”

Section: Methodsmentioning

confidence: 99%

“…Further, inflammation during tendon healing follows a temporal pattern and must be specifically modulated; early inflammation is necessary for healing but chronic inflammation diminishes tendon properties. Therefore, the establishment of a short inflammatory period is important but it must culminate to allow later stages of cell proliferation and tissue remodeling 16,17 …”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Pulsed electromagnetic field therapy alters early healing in a rat model of rotator cuff injury and repair: Potential mechanisms

Huegel

Chan

Weiss

et al. 2021

Journal Orthopaedic Research

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Rotator cuff repair failure remains common due to poor tendon healing, particularly at the enthesis. We previously showed that pulsed electromagnetic field (PEMF) therapy improved the mechanical properties of the rat supraspinatus tendon postoperatively. However, little is known about the mechanisms behind PEMF‐dependent contributions to improved healing in this injury model. The objective of this study was to determine the influence of PEMF treatment on tendon gene expression and cell composition, as well as bone microarchitecture and dynamic bone metabolism during early stages of healing. We hypothesized that PEMF treatment would amplify tendon‐healing related signaling pathways while mitigating inflammation and improve bone metabolism at the repair site. Rats underwent rotator cuff injury and repair followed by assignment to either control (non‐PEMF) or PEMF treatment groups. Gene and protein expression as well as tendon and bone histological assessments were performed 3, 7, 14, 21, and 28 days after injury. Gene expression data demonstrated an upregulation in the bone morphogenetic protein 2 signaling pathway and increases in pro‐osteogenic genes at the insertion, supporting important processes to re‐establish the tendon‐bone interface. PEMF also downregulated genes related to a fibrotic healing response. Anti‐inflammatory effects were demonstrated by both gene expression and macrophage phenotype. PEMF significantly increased the rate of kinetic bone formation directly adjacent to the tendon enthesis as well as the number of cuboidal surface osteoblasts (active osteoblasts) in the humeral head. This study has provided insight into how PEMF affects cellular and molecular processes in the supraspinatus tendon and adjacent bone after injury and repair.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Pulsed electromagnetic field therapy alters early healing in a rat model of rotator cuff injury and repair: Potential mechanisms

Huegel

Chan

Weiss

et al. 2021

Journal Orthopaedic Research

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“…To predict MSC-target interaction, the cell and matrix composition and immunological state of the target tissue are pivotal. However, due to the complex pathophysiological mechanisms in the course of inflammation, cell and matrix destruction as characteristics at the site of injury are inconsistent, depending on the type of tissue, the grade of cell destruction and the grade of local inflammatory reaction ( Ackerman et al, 2021 ; Scanzello and Goldring, 2021 ). Furthermore, though not being addressed within the present work, tissue specific resident MSC have already been shown to react context-sensitive in the respective pathophysiological microenvironment and may also be relevant for target interaction of applied MSC ( Costa-Almeida et al, 2019 ).…”

Section: Introductionmentioning

confidence: 99%

MSC in Tendon and Joint Disease: The Context-Sensitive Link Between Targets and Therapeutic Mechanisms

Roth¹,

Burk

Brehm³

et al. 2022

Front. Bioeng. Biotechnol.

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Mesenchymal stromal cells (MSC) represent a promising treatment option for tendon disorders and joint diseases, primarily osteoarthritis. Since MSC are highly context-sensitive to their microenvironment, their therapeutic efficacy is influenced by their tissue-specific pathologically altered targets. These include not only cellular components, such as resident cells and invading immunocompetent cells, but also components of the tissue-characteristic extracellular matrix. Although numerous in vitro models have already shown potential MSC-related mechanisms of action in tendon and joint diseases, only a limited number reflect the disease-specific microenvironment and allow conclusions about well-directed MSC-based therapies for injured tendon and joint-associated tissues. In both injured tissue types, inflammatory processes play a pivotal pathophysiological role. In this context, MSC-mediated macrophage modulation seems to be an important mode of action across these tissues. Additional target cells of MSC applied in tendon and joint disorders include tenocytes, synoviocytes as well as other invading and resident immune cells. It remains of critical importance whether the context-sensitive interplay between MSC and tissue- and disease-specific targets results in an overall promotion or inhibition of the desired therapeutic effects. This review presents the authors’ viewpoint on disease-related targets of MSC therapeutically applied in tendon and joint diseases, focusing on the equine patient as valid animal model.

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“…The degenerative features of the Achilles tendon on ultrasonography in type 2 diabetes were approximately 50%, while those in the control group were approximately 18.8% [12]. Tendinopathy in diabetes is a complex, multifactorial, pathological process involving altered macrophage function, angiogenic signaling, and neurotrophic signaling under both a chronic, low-grade inflammation and a high-glucose environment [13][14][15][16].…”

Section: Introductionmentioning

confidence: 99%

“…A recent study demonstrated that a high glucose environment in local tendon cells may dysregulate the resolution of inflammation [21]. Abnormal, excessive, or insufficient inflammation has serious detrimental effects on the tendon healing process [13].…”

Section: Introductionmentioning

confidence: 99%

Altered Differentiation of Tendon-Derived Stem Cells in Diabetic Conditions Mediated by Macrophage Migration Inhibitory Factor

Kim

Noh

Chae

et al. 2021

IJMS

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The purpose of our study was to evaluate the role of macrophage migration inhibitory factor (MIF) in the differentiation of tendon-derived stem cells (TdSCs) under hyperglycemic conditions. In the in vivo experiment, rats were classified into diabetic (DM) and non-DM groups depending on the intraperitoneal streptozotocin (STZ) or saline injection. Twelve-week after STZ injection, the supraspinatus tendon was harvested and prepared for histological evaluation and real-time reverse transcription polymerase chain reaction for osteochondrogenic (aggrecan, BMP-2, and Sox9) and tenogenic (Egr1, Mkx, scleraxis, type 1 collagen, and Tnmd) markers. For the in vitro experiment, TdSCs were isolated from healthy rat Achilles tendons. Cultured TdSCs were treated with methylglyoxal and recombinant MIF or MIF gene knockdown to determine the effect of hyperglycemic conditions and MIF on the differentiation function of TdSCs. These conditions were classified into four groups: hyperglycemic-control group, hyperglycemic-recombinant-MIF group, hyperglycemic-knockdown-MIF group, and normal-control group. The mRNA expression of osteochondrogenic and tenogenic markers was compared among the groups. In the in vivo experiment, the mRNA expression of all osteochondrogenic and tenogenic differentiation markers in the DM group was significantly higher and lower than that in the non-DM group, respectively. Similarly, in the in vitro experiments, the expression of all osteochondrogenic and tenogenic differentiation markers was significantly upregulated and downregulated, respectively, in the hyperglycemic-control group compared to that in the normal-control group. The hyperglycemic-knockdown-MIF group demonstrated significantly decreased expression of all osteochondrogenic differentiation markers and increased expression of only some tenogenic differentiation markers compared with the hyperglycemic-control group. In contrast, the hyperglycemic-recombinant-MIF group showed significantly increased expression of all osteochondrogenic differentiation markers, but no significant difference in any tenogenic marker level, compared to the hyperglycemic-control group. These results suggest that tendon homeostasis could be affected by hyperglycemic conditions, and MIF appears to alter the differentiation of TdSCs via enhancement of the osteochondrogenic differentiation in hyperglycemic conditions. These are preliminary findings, and must be confirmed in a further study.

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Metabolic Regulation of Tendon Inflammation and Healing Following Injury

Cited by 28 publications

References 94 publications

Pulsed electromagnetic field therapy alters early healing in a rat model of rotator cuff injury and repair: Potential mechanisms

Pulsed electromagnetic field therapy alters early healing in a rat model of rotator cuff injury and repair: Potential mechanisms

MSC in Tendon and Joint Disease: The Context-Sensitive Link Between Targets and Therapeutic Mechanisms

Altered Differentiation of Tendon-Derived Stem Cells in Diabetic Conditions Mediated by Macrophage Migration Inhibitory Factor

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