CD44 deficiency improves healing tendon mechanics and increases matrix and cytokine expression in a mouse patellar tendon injury model

Abstract Background: Tendon injury is a common but tough medical problem. Unsatisfactory clinical results have been reported in tendon repair using mesenchymal stem cells (MSCs) therapy, creating a need for a better strategy to induce MSCs to tenogenic differentiation. This study was designed to investigate the role of hypoxia in the tenogenic differentiation of MSCs in vitro and in vivo and to compare the tenogenic differentiation capacities of different MSCs under hypoxia condition in vitro. Methods: Adipose tissue-derived MSCs (AMSCs) and bone marrow-derived MSCs (BMSCs) were isolated and characterized by the expression of MSC-specific markers and tri-lineage differentiation. The expression of hypoxia induced factor-1 alpha (Hif-1α) and the proliferation of AMSCs and BMSCs were examined in order to confirm the establishment of hypoxia condition. qRT-PCR, western blot, and immunofluorescence staining were used to evaluate the expression of tendon-associated marker Col-1a1, Col-3a1, Dcn, and Tnmd in AMSCs and BMSCs under hypoxia and/or Tgf-β1 condition. In vivo, a patellar tendon injury model was established. Normoxic and hypoxic BMSCs were cultured and implanted. Histological, biomechanical and transmission electron microscopy analyses were performed to assess the improved healing effect of hypoxic BMSCs on tendon injury. Results: Hypoxia remarkably increased the expression of Hif-1α and the proliferation of AMSCs and BMSCs. Our in vitro results detected that hypoxia not only promoted a significant increase in tenogenic markers in both AMSCs and BMSCs compared with the normoxia group, but also showed higher inductility compared with Tgf-β1. In addition, hypoxic BMSCs exhibited higher potential of tenogenic differentiation than hypoxic AMSCs. Our in vivo results demonstrated that hypoxic BMSCs possessed better histological and biomechanical properties than those of normoxic BMSCs, as evidenced by histological scores, quantitative analysis of immunohistochemical staining for Col-1a1 and Tnmd, the range and average of collagen fibril diameters and patellar tendon biomechanical tests. Conclusions: These findings suggested that hypoxia may be a practical and reliable strategy to induce tenogenic differentiation of BMSCs for tendon repair and could enhance the effectiveness of MSCs therapy in treating tendon injury.

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Patellar Tendon Injury

Diagnostic Imaging: Musculoskeletal Trauma ◽

10.1016/b978-0-323-39253-2.50191-9 ◽

2016 ◽

pp. 808-813

Keyword(s):

Patellar Tendon ◽

Tendon Injury

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Hypoxia-Induced Mesenchymal Stem Cells Exhibit Stronger Tenogenic Differentiation Capacities and Promote Patellar Tendon Repair in Rabbits

Stem Cells International ◽

10.1155/2020/8822609 ◽

2020 ◽

Vol 2020 ◽

pp. 1-16

Author(s):

Guanyin Chen ◽

Wangqian Zhang ◽

Kuo Zhang ◽

Shuning Wang ◽

Yuan Gao ◽

...

Keyword(s):

Patellar Tendon ◽

Tendon Repair ◽

Biomechanical Properties ◽

Clinical Results ◽

Medical Problem ◽

Tendon Injury ◽

Tenogenic Differentiation ◽

Tgf Β1

Tendon injury is a common but tough medical problem. Unsatisfactory clinical results have been reported in tendon repair using mesenchymal stem cell (MSC) therapy, creating a need for a better strategy to induce MSCs to tenogenic differentiation. This study was designed to examine the effect of hypoxia on the tenogenic differentiation of different MSCs and their tenogenic differentiation capacities under hypoxia condition in vitro and to investigate the in vivo inductility of hypoxia in tenogenesis. Adipose tissue-derived MSCs (AMSCs) and bone marrow-derived MSCs (BMSCs) were isolated and characterized. The expression of hypoxia-induced factor-1 alpha (Hif-1α) was examined to confirm the establishment of hypoxia condition. qRT-PCR, western blot, and immunofluorescence staining were used to evaluate the expression of tendon-associated marker Col-1a1, Col-3a1, Dcn, and Tnmd in AMSCs and BMSCs under hypoxia condition, compared with Tgf-β1 induction. In vivo, a patellar tendon injury model was established. Normoxic and hypoxic BMSCs were cultured and implanted. Histological, biomechanical, and transmission electron microscopy analyses were performed to assess the improved healing effect of hypoxic BMSCs on tendon injury. Our in vitro results showed that hypoxia remarkably increased the expression of Hif-1α and that hypoxia not only promoted a significant increase in tenogenic markers in both AMSCs and BMSCs compared with the normoxia group but also showed higher inductility compared with Tgf-β1. In addition, hypoxic BMSCs exhibited higher potential of tenogenic differentiation than hypoxic AMSCs. Our in vivo results demonstrated that hypoxic BMSCs possessed better histological and biomechanical properties than normoxic BMSCs, as evidenced by histological scores, patellar tendon biomechanical parameters, and the range and average of collagen fibril diameters. These findings suggested that hypoxia may be a practical and reliable strategy to induce tenogenic differentiation of BMSCs for tendon repair and could enhance the effectiveness of MSCs therapy in treating tendon injury.

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Percutaneous reconstruction of patellar tendon using semitendinosus tendon in chronic patellar tendon injury — case series and outcome

The Knee ◽

10.1016/j.knee.2014.02.002 ◽

2014 ◽

Vol 21 (3) ◽

pp. 726-730 ◽

Cited By ~ 9

Author(s):

Jitesh Kumar Jain ◽

J.V.S. Vidyasagar ◽

Ravish Chabra

Keyword(s):

Patellar Tendon ◽

Case Series ◽

Tendon Injury ◽

Semitendinosus Tendon

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Knee Ultrasonography to Determine Risk for Noncontact Injuries in Collegiate American Football Players

The Journal of Knee Surgery ◽

10.1055/s-0039-1683953 ◽

2019 ◽

Vol 33 (07) ◽

pp. 666-672

Author(s):

Ryan A. Lewis ◽

Cristi R. Cook ◽

Patrick A. Smith ◽

James P. Stannard ◽

Rex L. Sharp ◽

...

Keyword(s):

Lower Extremity ◽

Patellar Tendon ◽

Screening Tool ◽

Knee Injuries ◽

Quadriceps Tendon ◽

Tendon Injury ◽

American Football ◽

Football Players ◽

Prospective Longitudinal Study ◽

Prospective Longitudinal

AbstractKnee ultrasonography has been used effectively as a screening tool for determining risk for knee injuries in athletes. Ultrasonography may be a valuable screening tool for relative risk of noncontact knee injuries that occur over a typical playing career in collegiate American football players. In this prospective longitudinal study, we evaluated American football players (n = 48) in an academic institution affiliated with the National Collegiate Athletic Association Division I athletic program. Players underwent comprehensive ultrasonography of both knees prior to beginning their collegiate careers. Anatomic structures were evaluated for presence and severity of abnormalities. Noncontact lower extremity injuries sustained over the collegiate career of the subjects were documented. Data were analyzed for correlations, differences in proportions, and odds ratio (OR). Seventy-nine percent of the athletes had at least one ultrasonographic abnormality, with quadriceps tendon (47.9%) and patellar tendon (39.6%) abnormalities predominating. Seventy-nine percent of players had at least one noncontact lower extremity injury (23.5% involving the knee) during their careers with an average of 2.8 injuries per career. The majority of injuries occurred in the second and third playing years. There was a significantly higher likelihood of patellar tendon injury based on the presence of patellar tendon ultrasonographic pathology (p = 0.024; OR = 11x). There was a significantly higher likelihood of quadriceps muscle–tendon injury based on the presence of quadriceps tendon ultrasonography pathology (p = 0.0012; OR = 140x). All athletes sustaining meniscal injuries had preexisting joint effusion but no preexisting ultrasonographic meniscal pathology. Knee ultrasonography along with patient history and complete physical examination may help reduce injury risk through education, prevention, and training programs.

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Effects of Time to Start Training After Acute Patellar Tendon Enthesis Injuries on Healing of the Injury in a Rabbit Model

The American Journal of Sports Medicine ◽

10.1177/0363546517712223 ◽

2017 ◽

Vol 45 (10) ◽

pp. 2405-2410 ◽

Cited By ~ 1

Author(s):

Lin Wang ◽

Kaiyu Xiong ◽

Bo Wang ◽

Xiaotian Liang ◽

Haiwei Li ◽

...

Keyword(s):

Patellar Tendon ◽

Rabbit Model ◽

Tendon Injury ◽

The Other ◽

Acute Injury ◽

Optimal Time ◽

Control Group ◽

Trabecular Thickness ◽

Training Groups ◽

Low Intensity

Background: A patellar tendon injury is a common injury in sports. The optimal time to start training after an acute, proximal patellar enthesis injury is still unclear. Hypothesis: The time to start training after an acute, proximal patellar enthesis injury significantly affects healing of the patellar tendon 4 weeks after the injury. Study Design: Controlled laboratory study. Methods: The left hindlimbs of 35 mature female rabbits were randomly assigned to 5 injury groups including a 4-week natural healing group (NH4W) and 4 training groups that started low-intensity training at 24 hours (POST24), 48 hours (POST48), 72 hours (POST72), and 96 hours (POST96) after an acute patellar tendon injury, with 7 limbs in each group. The right hindlimbs of the NH4W group were used as a control group (CON). An acute, proximal patellar enthesis injury was created in all injury groups. The training groups underwent low-intensity quadriceps training for 2 hours per day and 3 days per week for 4 weeks. Histological and radiographic data were collected and analyzed. Results: The cell densities of the training groups were significantly lower than those of the NH4W and CON groups ( P = .01). The fibrocartilage zone was significantly thicker in the POST24, POST48, and POST72 groups compared with the CON and NH4W groups and was the thickest in the POST24 group ( P = .01). The bone surface to bone volume ratio was significantly higher in all the injury groups compared with the CON group and in the POST24 group compared with the other groups ( P = .01). Trabecular thickness was significantly lower in all the injury groups compared with the CON group and in the POST24 group compared with the other groups ( P = .01). Conclusion: Resting without training in the first 96 hours after an acute patellar tendon enthesis injury resulted in the best recovery of cell density in the tendon enthesis 4 weeks after the injury. Starting training 96 hours after the injury resulted in the best recovery of fibrocartilage zone thickness. Starting training 48 to 96 hours after the injury resulted in the best healing of the bone component of the attachment site 4 weeks after the injury. The optimal time to start training may be longer than 96 hours after an acute patellar tendon enthesis injury for the best overall healing of the tendon enthesis 4 weeks after the injury. Clinical Relevance: A rest of a minimal 72 hours may be needed for the best healing of a patellar tendon enthesis after an acute injury. Future studies are needed to determine the optimal time to start training after an acute patellar tendon injury.

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Side to side differences in patellar tendon kinetics of the support limb during maximal instep soccer kicking

Baltic Journal of Health and Physical Activity ◽

10.29359/bjhpa.07.4.01 ◽

2015 ◽

Vol 7 (4) ◽

pp. 7-14

Author(s):

JONATHAN KENNETH SINCLAIR ◽

HANNAH SHORE ◽

STEPHEN ATKINS ◽

SARAH JANE HOBBS

Keyword(s):

Clinical Significance ◽

Patellar Tendon ◽

Tendon Injury ◽

Soccer Players ◽

Current Investigation ◽

Soccer Ball ◽

Paired Samples ◽

Increased Risk ◽

Bilateral Differences ◽

Kinetics Of

Background: Kicking actions have been implicated in the aetiology of soccer injuries, and the unilateral nature of kicking may influence this. The aim of the current investigation was to determine whether soccer players exhibit bilateral differences in support limb patellar tendon loads. Material/Methods: Fifteen male soccer players were examined whilst kicking a stationary soccer ball with both their dominant and non-dominant feet. Patellar tendon kinetics were obtained from each limb and then contrasted using paired samples t-tests. Results: Significant increases in patellar tendon kinetics were found when using the non-dominant limb. Conclusions: The findings from the current investigation have clinical significance and support the notion that kicking with the non-dominant limb may be associated with increased risk for patellar tendon injury aetiology.

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