The localized expression of extracellular matrix components in healing tendon insertion sites: an in situ hybridization study

Thomopoulos, Stavros; Hattersley, Gary; Rosen, Vicki; Mertens, Michelle; Galatz, Leesa M.; Williams, Gerald R.; Soslowsky, Louis J.

doi:10.1016/s0736-0266(01)00144-9

Cited by 226 publications

(208 citation statements)

References 23 publications

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“…Animals did not need to be restrained for this task as they willingly drank fluid from the syringe after their training period. All animals then underwent bilateral supraspinatus detachment and repair surgeries as described previously in detail [3,27]. Buprenorphine was administered subcutaneously to all animals at a dose of 0.05 mg/kg immediately before surgery and then every 8 to 12 hours for the next 2 days.…”

Section: Methodsmentioning

confidence: 99%

The Detrimental Effects of Systemic Ibuprofen Delivery on Tendon Healing Are Time-Dependent

Connizzo

Yannascoli

Tucker

et al. 2014

Clinical Orthopaedics &Amp; Related Research

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Background Current clinical treatment after tendon repairs often includes prescribing NSAIDs to limit pain and inflammation. The negative influence of NSAIDs on bone repair is well documented, but their effects on tendon healing are less clear. While NSAIDs may be detrimental to early tendon healing, some evidence suggests that they may improve healing if administered later in the repair process.Questions/purposes We asked whether the biomechanical and histologic effects of systemic ibuprofen administration on tendon healing are influenced by either immediate or delayed drug administration. Methods After bilateral supraspinatus detachment and repair surgeries, rats were divided into groups and given ibuprofen orally for either Days 0 to 7 (early) or Days 8 to 14 (delayed) after surgery; a control group did not receive ibuprofen. Healing was evaluated at 1, 2, and 4 weeks postsurgery through biomechanical testing and histologic assessment. Results Biomechanical evaluation resulted in decreased stiffness and modulus at 4 weeks postsurgery for early ibuprofen delivery (mean ± SD [95% CI]: 10.8 ± 6.4 N/mm [6.7-14.8] and 8.9 ± 5.9 MPa [5.4-12.3]) when compared to control repair .2]) (p = 0.003 and 0.013); however, there were no differences between the delayed ibuprofen group (18.1 ± 7.4 N/mm [14.2-22.1] and 11.5 ± 5.6 MPa [8.2-14.9]) and the control group. Histology confirmed mechanical results with reduced fiber reorganization over time in the early ibuprofen group.

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Section: Methodsmentioning

confidence: 99%

The Detrimental Effects of Systemic Ibuprofen Delivery on Tendon Healing Are Time-Dependent

Connizzo

Yannascoli

Tucker

et al. 2014

Clinical Orthopaedics &Amp; Related Research

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“…Although increases of aggrecan and biglycan in tendons have been implicated in early tendon healing process [104], the changes of other type of proteoglycans in tendinopathy are different to those in normal and healing tendons ( Table 2). Very little is known about the changes in noncollagen glycoproteins in tendinopathy.…”

Section: Extracellular Matrix (Ecm)mentioning

confidence: 99%

The Basic Science of Tendinopathy

Murrell

2008

Clinical Orthopaedics &Amp; Related Research

299

247

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Tendinopathy is a common clinical problem with athletes and in many occupational settings. Tendinopathy can occur in any tendon, often near its insertion or enthesis where there is an area of stress concentration, and is directly related to the volume of repetitive load to which the tendon is exposed. Recent studies indicate tendinopathy is more likely to occur in situations that increase the ''dose'' of load to the tendon enthesis -including increased activity, weight, advancing age, and genetic factors. The cells in tendinopathic tendon are rounder, more numerous, and show evidence of oxidative damage and more apoptosis. These cells also produce a matrix that is thicker and weaker with more water, more immature and cartilage-like matrix proteins, and less organization. There is now evidence of a population of regenerating stem cells within tendon. These studies suggest prevention of tendinopathy should be directed at reducing the volume of repetitive loads to below that which induces oxidative-induced apoptosis and cartilage-like genes. The management strategies might involve agents or cells that induce tendon stem cell proliferation, repair and restoration of matrix integrity.

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“…Moreover, chondrocytes are arranged in rows and the collagen fibers line up parallel to the long axis of the tendon [2,5]. Biomechanically, this 4-zone structure and the arrangement of the collagen fibers not only provide for a gradual transition of tension but also enable the rotator cuff to withstand shear moments involved with shoulder motion thus averting mechanical failure [20,34]. Little precise information exists on enthesis formation after surgical repair.…”

Section: I: Koike Et Al I Journal Of Orthopaedic Research 23 11005 Imentioning

confidence: 99%

“…Enthesis formation following experimental repair has been studied in a number of animal models [22,25,28,34,36,39] but the small sample size and qualitative nature of the outcome measures limited the generalization of their results. In 2002, our group observed advanced histologic reformation of the fibrocartilage 8 weeks after surgical attachment of supraspinatus tendon into the humerus in 7 rabbits [41].…”

Section: I: Koike Et Al I Journal Of Orthopaedic Research 23 11005 Imentioning

confidence: 99%

Formation of a new enthesis after attachment of the supraspinatus tendon: A quantitative histologic study in rabbits

2005

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Purpose. To quantify in a longitudinal study non-chondrocytic cells and chondrocytes, tissular architecture as well as extracellular matrix restoration during the formation of an enthesis following supraspinatus tendon attachment to the humerus. Methods. In 89 rabbits, one supraspinatus fibrocartilaginous enthesis was resected and the tendon either attached to the greater tuberosity (n = 75) or not attached ( n = 14). The animals were sacrificed after 2, 6, 8, 12 or 24 weeks. The operated and contralateral shoulders were processed for histologic sections. Number of non-chondrocytes, chondrocytes and alignment of chondrocytes in rows were assessed histologically. Extracellular matrix restoration was measured based on ( 1 ) area of toluidine blue metachromasia indicating proteoglycan content and (2) on area of diffracted polarized light indicating spatial collagen fiber alignment. Results. In the attached tendon, the number of non-chondrocytic cells sharply increased at 2 weeks, progressively decreased thereafter but remained higher than controls at all time points. Chondrocytes appeared at 2 weeks and their number reached control levels by 6 weeks (136 f 14 vs 144 5 15 controls, p .05). The percentage of chondrocytes aligned in rows increased from 19 k 4% at 2 weeks to reach near normal values at 24 weeks (71 f 3% vs 78 5 2% controls, p > .05). Area of metachromasia increased from 0.1 f 0.1 mm2 at 2 weeks to 3.8 k 0.3 mm2 at 24 weeks, still below contralateral enthesis levels (4.6 f 0.1 mm2, p < .05). Area of diffracted polarized light enlarged from 12 5 2 x lo3 pm2 at 2 weeks to 151 k 19 x lo3 pm2 at 24 weeks, still significantly smaller than contralateral levels (177 k 13 x lo3 pm', p < .05). Neither chondrocytes nor metachromasia were observed in the non-attached tendons. Conclusion. A new enthesis was formed after attachment of the supraspinatus tendon into bony trough. Histomorphometry allowed to document extensive non-chondrocytic proliferation that was followed by appearance of chondrocytes and their spatial organization, a process was complete by 24 weeks. Extracellular matrix formation as well as spatial alignment of collagen fibers were delayed and not complete by 24 weeks. This first longitudinal investigation on the formation of the supraspinatus enthesis using quantitative outcome measures cautions against too early and too aggressive a rehabilitation program.

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The localized expression of extracellular matrix components in healing tendon insertion sites: an in situ hybridization study

Cited by 226 publications

References 23 publications

The Detrimental Effects of Systemic Ibuprofen Delivery on Tendon Healing Are Time-Dependent

The Detrimental Effects of Systemic Ibuprofen Delivery on Tendon Healing Are Time-Dependent

The Basic Science of Tendinopathy

Formation of a new enthesis after attachment of the supraspinatus tendon: A quantitative histologic study in rabbits

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