A Comparative Study on the Biomechanical and Histological Properties of Bone-to-Bone, Bone-to-Tendon, and Tendon-to-Tendon Healing: An Achilles Tendon-Calcaneus Model in Goats.

BACKGROUND: Surgical repair around the bone-tendon insertion (BTI) may involve bone-to-bone (BB), bone-to-tendon (BT), or tendon-to-tendon (TT) reattachment with varying healing outcome. HYPOTHESIS: The repair of Achilles tendon-calcaneus (ATC) by reattachment of homogeneous tissue (BB or TT) would heal faster, with respect to tensile properties at the healing complex, than those of reattachment of heterogeneous tissues (BT) over time. STUDY DESIGN: Controlled laboratory study. METHODS: Forty-seven adolescent male Chinese goats were divided into BB, BT, and TT groups. Osteotomy of the calcaneus, reattachment of Achilles tendon to the calcaneus after removal of the insertion, and tenotomy of the Achilles tendon were performed to simulate BB, BT, and TT repair, respectively. The ATC healing complexes were harvested at 6, 12, or 24 weeks postoperatively. Mechanical and morphological properties of the healing ATC complexes were assessed by tensile testing and qualitative histology, respectively. The contralateral intact ATC complex was used as the control. RESULTS: Failure load of BT was 33.4% lower than that of TT (P = .0243) at week 12. Ultimate strength of BT was 50.2% and 45.3% lower than that of TT at weeks 12 (P = .0002) and 24 (P = .0001), respectively. Tissue morphological characteristics of the BB and TT groups showed faster remodeling. The BT group showed limited regeneration of fibrocartilage zone and excessive formation of fibrous tissue at the healing interface. CONCLUSION: BTI repair between homogeneous tissues (BB and TT healing) showed better healing quality with respect to mechanical and histological assessments than did healing between heterogeneous tissues (BT healing). CLINICAL RELEVANCE: Anatomic reconstruction of ATC complex injury may be a primary concern when selecting the proper surgical approach. However, it is recommended to select fracture fixation (BB) or tendon repair (TT) instead of bone-tendon reattachment (BT) if possible to ensure better outcome at the healing interface.

Extracorporeal shockwave enhanced regeneration of fibrocartilage in a delayed tendon-bone insertion repair model.

Fibrous tissue is often formed in delayed healing of tendon bone insertion (TBI) instead of fibrocartilage. Extracorporeal shockwave (ESW) provides mechanical cues and upregulates expression of fibrocartilage-related makers and cytokines. We hypothesized that ESW would accelerate fibrocartilage regeneration at the healing interface in a delayed TBI healing model. Partial patellectomy with shielding at the TBI interface was performed on 32 female New Zealand White Rabbits for establishing this delayed TBI healing model. The rabbits were separated into the control and ESW group for evaluations at postoperative week 8 and 12. Shielding was removed at week 4 and a single ESW treatment was applied at week 6. Fibrocartilage regeneration was evaluated histomorphologically and immunohistochemically. Vickers hardness of the TBI matrix was measured by micro-indentation. ESW group showed higher fibrocartilage area, thickness, and proteoglycan deposition than the control in week 8 and 12. ESW increased expression of SOX9 and collagen II significantly in week 8 and 12, respectively. ESW group showed a gradual transition of hardness from bone to fibrocartilage to tendon, and had a higher Vickers hardness than the control group at week 12. In conclusion, ESW enhanced fibrocartilage regeneration at the healing interface in a delayed TBI healing model.

Extracorporeal shockwave therapy for treatment of delayed tendon-bone insertion healing in a rabbit model: a dose-response study.

BACKGROUND: Tendon-bone insertion (TBI) consists of both hard and soft tissues. TBI injury with delayed repair is not uncommon. High-dose extracorporeal shockwave (ESW) is effective for treating nonunion fracture, whereas low-dose ESW is used for tendinopathy therapy. The dosing effect of ESW on delayed TBI healing is lacking. HYPOTHESIS: Low-dose ESW might have a healing enhancement effect comparable to that of high-dose ESW in treating delayed TBI healing. STUDY DESIGN: Controlled laboratory study. METHODS: Partial patellectomy was adopted to create a delayed TBI healing model by shielding the healing interface between tendon and bone. Ninety-six female New Zealand White rabbits with unilateral delayed TBI healing at the knee joint were divided into 3 groups: controls, low-dose ESW (LD-ESW; 0.06 mJ/mm(2), 4 Hz, 1500 impulses), and high-dose ESW (HD-ESW; 0.43 mJ/mm(2), 4 Hz, 1500 impulses). The TBI shielding was removed at week 4 after partial patellectomy, followed by treatment with control or ESW at week 6. The rabbits were euthanized at week 8 and week 12 for radiological, microarchitectural, histological, and mechanical assessments of healing tissues. RESULTS: Radiologically, both the LD-ESW group and the HD-ESW group showed larger new bone area than the controls at week 8 and week 12. Microarchitectural measurements showed that the LD-ESW and HD-ESW groups had larger new bone volume than the controls at week 12. Histological assessments confirmed osteogenesis enhancement. Both the LD-ESW and HD-ESW groups showed significantly higher failure load at the TBI healing complex than the control group at week 12. No significant difference was detected between the 2 ESW treatment groups at week 8 or week 12. CONCLUSION: Extracorporeal shockwave, a unique noninvasive physical modality, had similar effects between the low and high dose for treating delayed TBI healing. CLINICAL RELEVANCE: Low-dose ESW for TBI delayed healing might be more desirable and have better compliance in clinical applications.

High-resolution MR imaging of talar osteochondral lesions with new classification.

PURPOSE: Retrospective review of high-resolution MR imaging features of talar dome osteochondral lesions and development of new classification system based on these features. MATERIAL AND METHODS: Over the past 7 years, 70 osteochondral lesions of the talar dome from 70 patients (49 males, 21 females, mean age 42 years, range 15-62 years) underwent high-resolution MR imaging with a microscopy coil at 1.5 T. Sixty-one (87%) of 70 lesions were located on the medial central aspect and ten (13%) lesions were located on the lateral central aspect of the talar dome. Features evaluated included cartilage fracture, osteochondral junction separation, subchondral bone collapse, bone:bone separation, and marrow change. Based on these findings, a new five-part grading system was developed. Signal-to-noise characteristics of microscopy coil imaging at 1.5 T were compared to dedicated ankle coil imaging at 3 T. RESULTS: Microscopy coil imaging at 1.5 T yielded 20% better signal-to-noise characteristics than ankle coil imaging at 3 T. High-resolution MR revealed that osteochondral junction separation, due to focal collapse of the subchondral bone, was a common feature, being present in 28 (45%) of 61 medial central osteochondral lesions. Reparative cartilage hypertrophy and bone:bone separation in the absence of cartilage fracture were also common findings. Complete osteochondral separation was uncommon. A new five-part grading system incorporating features revealed by high-resolution MR imaging was developed. CONCLUSIONS: High-resolution MRI reveals clinically pertinent features of talar osteochondral lesions, which should help comprehension of symptomatology and enhance clinical decision-making. These features were incorporated in a new MR-based grading system. Whenever possible, symptomatic talar osteochondral lesions should be assessed by high-resolution MR imaging.

Use of allogeneic scaffold-free chondrocyte pellet in repair of osteochondral defect in a rabbit model.

Cell-based therapies are currently being used in treating osteochondral defect (OCD), but technical advances are needed to tackle the problems of scaffold and grafting technique. This study aimed to test the potential of allogeneic scaffold-free bioengineered chondrocyte pellet (BCP) in treating OCD. BCP was fabricated from rabbit costal cartilage and implanted into 3 mm × 3 mm OCD in medial femoral condyle of 20 rabbits. Samples were harvested at 2, 4, 8, and 16 weeks for histology, histological scoring and histomorphometric analysis. At treated side, cartilage score was significantly better at week 4 (p = 0.027), and cartilage thickness measured in histomorphometric analysis was significantly thicker at week 4 (p = 0.028) and week 16 (p = 0.028) compared to the empty controls. At treated side, bone score remained significantly lower from week 8 onwards (p = 0.024 at week 8, p = 0.02 at week 16) whereas bone area was significantly smaller from week 4 onwards compared to the empty controls (p = 0.028 at week 4, 8, 16). No immunorejection was observed throughout the experiment. The results demonstrated that the BCP enhanced cartilage repair at early stage. Press-fitting of allogeneic BCP was a simple method for OCD repair without immunorejection. Further optimization of the treatment is required before clinical application.

Small field-of-view surface coil mr imaging of talar osteochondral lesions.

BACKGROUND: Osteochondral lesion (OCL) treatment is based on patient symptoms, lesion size, and lesion stability. MRI of talar OCL identifies the presence and the characteristics of the lesion and attempts to establish lesion stability. We report our experience that the depiction of OCL can be improved by using a small field-of-view (FOV) surface coil. MATERIALS AND METHODS: We studied 24 patients (25 lesions) with OCLs of the talar dome. Standard FOV MRI followed by small FOV MRI of the ankle was performed at 1.5-T. Standard FOV MRI was taken using a quadrature knee coil or a 21 cm x 53 cm circularly flexible coil. A 4-cm circular polarized receiver surface coil was used for small FOV imaging. Twelve aspects characteristics of OCLs were assessed, including lesion matrix, margin characteristics, lesion cortical surface, cartilage surface, cartilage depth, cartilage signal, cartilage integrity, and osteochondral gap. RESULTS: Small FOV MRI provided more detailed morphological information of talar OCL. The following differences were noted. Small FOV coil imaging reclassified cortical surface from flush to depressed in seven cases and from unclear in two cases to flush in one case and proud in the other. Small FOV coil imaging reclassified cartilage integrity from unclear to intact in 16 cases and from unclear to fracture in three cases. For assessment of osteochondral gap, small FOV coil MR imaging reclassified from absent to present in two cases and from unclear to absent in one case. For osteochondral fragment, small FOV coil MR imaging reclassified assessment from absent to present in three cases and from unclear to absent in three cases. CONCLUSION: Small FOV coil improved visualization of the talar OCL.

Grafted tendon healing in tibial tunnel is inferior to healing in femoral tunnel after anterior cruciate ligament reconstruction: a histomorphometric study in rabbits.

PURPOSE: This study aimed to test whether graft healing in the tibial tunnel was inferior to that in the femoral tunnel after anterior cruciate ligament (ACL) reconstruction in rabbits. METHODS: Surgical reconstruction by use of the digital extensor tendon in the bone tunnel was performed in 18 rabbits. The rabbits were killed at weeks 2, 6, and 12 postoperatively, with 6 at each time point, for histologic examination. RESULTS: The transiently formed cartilaginous interface was gradually mineralized during re-establishment of direct tendon-to-bone integration, which was observed significantly less in the tibial tunnel than in the femoral tunnel (P < .05). The cell density of the graft was significantly lower in the tibial tunnel than that in the femoral tunnel at weeks 2 and 6 postoperatively (P < .05 for both). An increase in the immature type III collagen content was accompanied by a decrease in graft collagen fiber organization, with healing over time in both the femoral and tibial tunnels. The collagen fiber organization of the graft was significantly poorer in the tibial tunnel than that in the femoral tunnel at week 12 after surgery (P < .05). CONCLUSIONS: Grafted tendon healing in the tibial tunnel was inferior to that in the femoral tunnel at the tendon-to-bone interface and with regard to the grafted tendon within the bone tunnel after ACL reconstruction in rabbits. CLINICAL RELEVANCE: Future biopsy study is desirable to test whether this observation was valid clinically, which might provide a scientific basis for therapeutic targets to improve the outcome of ACL surgery.

Osteogenesis induced by extracorporeal shockwave in treatment of delayed osteotendinous junction healing.

Healing at the osteotendinous junction (OTJ) is challenging in orthopedic surgery. The present study aimed to test extracorporeal shockwave (ESW) in treatment of a delayed OTJ healing. Twenty-eight rabbits were used for establishing a delayed healing (DH) model at patella-patellar-tendon (PPT) complex after partial patellectomy for 4 weeks and then were divided into DH and ESW groups. In the ESW group, a single ESW treatment was given at postoperative week 6 to the PPT healing complex. The samples were harvested at week 8 and 12 for radiographic and histological evaluations with seven samples for each group at each time point. Micro-CT results showed that new bone volume was 1.18 +/- 0.61 mm(3) in the ESW group with no measurable new bone in the DH group at postoperative week 8. Scar tissue formed at the OTJ healing interface of the DH group, whereas ESW triggered high expression of VEGF in hypertrophic chondrocytes at week 8 and regeneration of the fibrocartilage zone at week 12 postoperatively. The accelerated osteogenesis could be explained by acceleration of endochondral ossification. In conclusion, ESW was able to induce osteogenesis at OTJ with delayed healing with enhanced endochondral ossification process and regeneration of fibrocartilage zone. These findings formed a scientific basis to potential clinical application of ESW for treatment of delayed OTJ healing.

The effect of glucocorticoids on tendon cell viability in human tendon explants.

BACKGROUND AND PURPOSE: Previous studies on the culture of human tenocytes have shown that dexamethasone and triamcinolone reduce cell viability, suppress cell proliferation, and reduce collagen synthesis. However, such cell cultures lack the extracellular matrix and three-dimensional structure of normal tendons, which affects their response to stimuli. We established a human tendon explant culture system and tested the effects of dexamethasone and triamcinolone on cell viability. METHODS: Primary human tendon explant cultures were prepared from healthy hamstring tendons. Tendon strips were harvested from hamstring tendons and cultured in 24-well plates in Dulbecco's modification of Eagle's Medium (DMEM) supplemented with 2% fetal calf serum. The tendon explants were treated with 0 microM (control), 10 microM, or 100 microM dexamethasone sodium phosphate or 0 microM (control), 10 microM, or 100 microM triamcinolone acetonide in DMEM for 96 h. Cell viability was measured by Alamar blue assay before and after glucocorticoid treatment. RESULTS: Incubation with 10 microM and 100 microM dexamethasone reduced cell viability in human tendon explants by 35% and 45%, respectively, as compared to a 6% increase in the controls (p = 0.01, mixed-effects ANOVA). Triamcinolone at 10 microM and 100 microM reduced cell viability by 33% and 36%, respectively, as compared to a 9% increase in the controls (p = 0.07, mixed-effects ANOVA). INTERPRETATION: Human tendon explant cultures can be used to study the effects of glucocorticoids on human tendon. Dexamethasone and triamcinolone suppress the cell viability of human tendon in its natural 3-dimensional environment with matrix anchorage. Human tendon explant cultures provide a species-specific model for further investigation of the effects of glucocorticoids on the metabolism of the extracellular matrix of human tendon, and on its mechanical properties.

Influence of bone adaptation on tendon-to-bone healing in bone tunnel after anterior cruciate ligament reconstruction in a rabbit model.

Anterior cruciate ligament (ACL) reconstruction with placement of grafted tendon in bone tunnel is a common surgical procedure. Bone tunnel creation may result in stress shielding of postero-lateral regions of tibial tunnel. The present study was designed to characterize the changes of peri-graft bone and compare with tendon-to-bone (T-B) healing in spatial and temporal manners after ACL reconstruction in rabbit. Surgical reconstruction using digital extensor tendon in bone tunnel was performed on 48 rabbits. Twelve rabbits were sacrificed at 0, 2, 6, and 12 weeks postoperatively for radiological and histological examinations. Bone mass and microarchitecture at the anterior, posterior, medial, and lateral regions of tunnel wall at distal femur and proximal tibia were evaluated. Using peripheral quantitative computed tomography, a 26, 22, and 42% decrease in bone mineral density (BMD) relative to baseline was present in the medial region of the femoral tunnel and the posterior and lateral regions of the tibial tunnel, respectively, at week 12 postoperatively (p < 0.05). It was accompanied by a decrease in trabecular number and increase in trabecular spacing, the shift of platelike to rodlike trabeculae, and loss of anisotropy under micro-computed tomography evaluation. This finding was echoed by histology showing increased osteoclastic activities and poor T-B healing in these regions. In conclusion, the postoperative bone loss and associated poor T-B healing was region-dependent, which may result from adaptive changes after tunnel creation.

Articular cartilage increases transition zone regeneration in bone-tendon junction healing.

The fibrocartilage transition zone in the direct bone-tendon junction reduces stress concentration and protects the junction from failure. Unfortunately, bone-tendon junctions often heal without fibrocartilage transition zone regeneration. We hypothesized articular cartilage grafts could increase fibrocartilage transition zone regeneration. Using a goat partial patellectomy repair model, autologous articular cartilage was harvested from the excised distal third patella and interposed between the residual proximal two-thirds bone fragment and tendon during repair in 36 knees. We evaluated fibrocartilage transition zone regeneration, bone formation, and mechanical strength after repair at 6, 12, and 24 weeks and compared them with direct repair. Autologous articular cartilage interposition resulted in more fibrocartilage transition zone regeneration (69.10% +/- 14.11% [mean +/- standard deviation] versus 8.67% +/- 7.01% at 24 weeks) than direct repair at all times. There was no difference in the amount of bone formation and mechanical strength achieved. Autologous articular cartilage interposition increases fibrocartilage transition zone regeneration in bone-tendon junction healing, but additional research is required to ascertain the mechanism of stimulation and to establish the clinical applicability.

Low-intensity pulsed ultrasound on tendon healing: a study of the effect of treatment duration and treatment initiation.

BACKGROUND: Low-intensity pulsed ultrasound has been reported to be effective in promoting tendon healing. However, its optimal time and duration has not yet been determined. HYPOTHESIS: Tendons at different stages of healing may respond differently to low-intensity pulsed ultrasound. In the present study, the timing effects of low-intensity pulsed ultrasound on tendon healing were investigated in a rat model with a patellar tendon graft harvest lesion. STUDY DESIGN: Controlled laboratory study. METHODS: Sixty Sprague-Dawley rats underwent central third patellar tendon donor site harvest. Low-intensity pulsed ultrasound sonication was then delivered to the injured knees at day 1, 14, or 28 after harvest for 2, 4, or 6 weeks. Tendon samples were harvested at day 14, 28, and 42 after lesion for histological examination and mechanical testing. RESULTS: A 2-week session of low-intensity pulsed ultrasound applied from day 1 postlesion (D1-2W) significantly improved the ultimate mechanical strength of the healing tendons from 23.1 +/- 8.5 MPa to 36.6 +/- 9.0 MPa. Low-intensity pulsed ultrasound did not improve healing when it was given at later stages in D15-2W and D29-2W. When low-intensity pulsed ultrasound treatment was extended from 2 weeks (D1-2W) to 4 weeks (D1-4W) or 6 weeks (D1-6W), the beneficial effects on tendon healing became insignificant. Histological examination showed that low-intensity pulsed ultrasound sonication at late healing stages may disturb remodeling with a poor collagen fiber alignment. CONCLUSION: Low-intensity pulsed ultrasound promoted restoration of mechanical strength and collagen alignment in healing tendons only when applied at early healing stages. CLINICAL RELEVANCE: The present findings indicate that low-intensity pulsed ultrasound may be an effective treatment to reduce tendon donor site morbidity.

Expression of transforming growth factor beta isoforms and their roles in tendon healing.

Transforming growth factor beta (TGF-beta) plays active roles in tendon healing. However, the differential effects of TGF-beta isoforms on tendon healing have not been investigated. In cultured tendon fibroblasts, we tested the effects of TGF-beta1, beta2, and beta3 on the mRNA levels of COL1A1 and COL3A1 by quantitative real-time polymerase chain reaction. We also investigated the expression of TGF-beta isoforms, TGF-beta receptors, procollagen Type I and Type III in a rat model of tendon healing. We found that TGF-beta3 exhibited the highest potency in stimulating COL1A1 and COL3A1. TGF-beta1 exerted antagonistic effects to TGF-beta2 and beta3. All TGF-beta isoforms and procollagen Type I were confined to the edges of the healing tendon at day 28 postinjury. Our results indicated that interaction of TGF-beta isoforms exist in the regulation of collagen synthesis in tendon fibroblasts. Their effects may be further complicated by uneven spatial distribution of TGF-beta and TGF-beta receptors in healing tendons.

Is cultured tendon fibroblast a good model to study tendon healing?

Cultured tendon fibroblasts (CTFs) from intact explants are widely used to study tendon healing in vitro. The significance of these findings may rely on similarities between CTFs and healing tendon fibroblasts in situ. Our purpose was to compare CTFs with fibroblasts cultured from healing tendons. We cultured CTFs from intact and healing tendons at day 7 and day 14 postinjury in a rat model of patellar donor site injury. The mRNA expression of COL1A1, COL3A1, decorin, and biglycan, with or without supplementation of 1 ng/mL TGF-beta1, was compared by quantitative real-time RT-PCR. The expression of proliferation cell nuclear antigen (PCNA) and alpha-smooth muscle actin (alpha-SMA) was determined by immunostain. COL3A1 and decorin mRNA in CTFs was lower as compared to day 7 healing fibroblasts, but its biglycan mRNA level was higher than day 14 healing fibroblasts. TGF-beta1 increased COL1A1 and decorin mRNA in CTFs, but decreased the mRNA of all four genes in day 7 healing tendon fibroblasts. CTFs exhibited lower PCNA immunopositivity as compared to day 7 and day 14 healing fibroblasts, but a higher alpha-SMA immunopositivity than cultured day 14 healing fibroblasts. These findings showed that CTFs did not resemble healing tendon cells with respect to major cellular activities related to tendon healing. Thus, fibroblasts from healing tendon may be a more appropriate model for studying cellular activities in tendon healing.

Predictors for mortality after lower-extremity amputations in geriatric patients.

BACKGROUND: The identification of independent predictors for operative and long-term mortality after lower-extremity amputations in the geriatric population would allow targeted management for high-risk patients and appropriate allocation of resources. METHODS: Univariate and multivariate logistic regression analyses were used to identify independent predictors for operative mortality. Life tables and Kaplan-Meier survival curves were generated. Independent predictors for long-term mortality were tested by log-rank test followed by Cox regression analysis. RESULTS: Female gender, congestive heart failure, and high-level amputation were identified as independent predictors for operative mortality (odds ratios 4.14, 4.59, and 4.77, respectively). The logistic regression model showed good calibration and discriminative power. Female gender, high-level amputation, cerebrovascular accident, congestive heart failure, noncommunity ambulation, and institutionalization before amputation were associated with an increased risk for long-term mortality. However, only high-level amputation, congestive heart failure, and noncommunity ambulation remained as independent risk factors after Cox regression analysis (relative risks 1.68, 2.08, and 2.10, respectively). CONCLUSIONS: Extra care should be given to patients identified with independent predictors for operative and long-term mortality.

Rotational stability of Seidel nail distal locking mechanism.

The intramedullary distal locking mechanism in the Seidel nail uses interference fit, avoiding the need of a screw traversing soft tissue and the risk of neurovascular injury. However, there is concern for its rotational stability. This study was designed to test the rotational stability of the distal locking mechanism under the least stable conditions. A transverse osteotomy was performed 10 cm proximal to the trochlea in 10 cadaveric humeri, followed by insertion of a 9 mm diameter Seidel nail and distally locked. The proximal humeral segments were removed. Rotational test to failure was performed with a material testing machine. The initial medullary diameter and the amount of flange spread measured 9.95 mm and 11.28 mm, respectively. Most of the flanges were found to be incompletely deployed. Failure occurred by slippage of the flanges. The average failure torque and torsional stiffness of the nail bone construct tested were 0.262 N m and 0.070 N m/ degrees . The Seidel nail distal locking mechanism has low rotational stability on mechanical testing. However, the low failure torque tested in vitro does not always preclude successful fracture healing and a good clinical outcome. Whether the presence of rotational micro motion would be beneficial to bone healing would need further investigation.

Modified flexor hallucis longus transfer for Achilles insertional rupture in elderly patients.

Elderly patients with symptomatic Achilles tendinopathy who develop insertional ruptures develop are at risk of persistent pain and poor functional outcome. Extensive debridement of the tendinopathy creates a defect that adds to the difficulty of Achilles insertional rupture repair. Complete excision of the tendinopathy segment was proposed to minimize persistent pain. Reconstruction of the defect using modified flexor hallucis longus transfer might better restore Achilles function. Five patients older than 50 years (mean age, 58.8 years) who had symptomatic Achilles tendinopathy and subsequently had insertional ruptures were treated. The outcome was assessed at an average of 28.8 months after the reconstruction. There was good pain relief. All patients were able to do single-leg stance. Cybex isokinetic testing showed plantar flexion peak torque deficits of 10.9% and 3.9% when tested at 60 degrees /second and 120 degrees /second, respectively. The Functional Ambulation Performance score indicated a near normal gait pattern. The American Orthopaedic Foot and Ankle Society hindfoot score improved from 64.4 to 94.4. There was no major surgical complication and no re-rupture. Excision of Achilles tendinopathy segment followed by modified flexor hallucis longus transfer can achieve good pain relief and functional recovery in elderly patients with symptomatic Achilles tendinopathy who have Achilles insertional ruptures develop.

Glucocorticoids suppress proteoglycan production by human tenocytes.

BACKGROUND: The role of glucocortiocid injection therapy in spontaneous tendon rupture is controversial. We hypothesized that glucocorticoids suppress proteoglycan production in tendon and studied the in vitro effects of dexamethasone and triamcinolone on proteoglycan production by cultured human tenocytes. MATERIAL AND METHODS: We obtained primary cultures of human tenocytes from explants of healthy human patellar tendon. The human tenocytes were treated with 1 microM dexamethasone or 1 microM triamcinolone. The amount of proteoglycan production was measured by 35S-sulfate incorporation assay and compared with control cultures. The reversibility of the effect of dexamethasone by co-incubation with 10 ng platelet-derived growth factor (PDGFBB) was also tested. RESULTS: Treatment with 1 microM triamcinolone reduced the amount of 35S-sulfate incorporation to 80% of control cultures (p = 0.007), whereas 1 microM dexamethasone reduced it to 72% (p = 0.01). Co-incubation of 10 ng/mL PDGFBB with 1 microM dexamethasone returned the 35S-sulfate incorporation to a level that was significantly higher than for dexamethasone treatment alone (108%; p = 0.01). INTERPRETATION: Glucocorticoids suppressed proteoglycan production in cultured human tenocytes. The suppression by dexamethasone was reversed by simultaneous addition of PDGFBB. Suppressed proteoglycan production may affect the viscoelastic properties of tendon and increase the risk of spontaneous rupture.

Triamcinolone suppresses human tenocyte cellular activity and collagen synthesis.

Glucocorticoid injection is widely used in tendon disorders. Despite previous studies on the histologic and biomechanical changes in tendons after glucocorticoid injections, the role of glucocorticoid in tendon rupture still is controversial. It was hypothesized that glucocorticoid has a direct deleterious effect on human tenocytes, suppressing its cellular activity and collagen production. Primary cultures of human tenocytes were obtained from explants of healthy patellar tendon harvested during anterior cruciate ligament reconstructions. The effects on cell viability and cell proliferation were measured by [3-(4,5-demethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay and 5-bromo-deoxyuridine incorporations. The effect on collagen synthesis was measured by H-proline incorporation assay. Triamcinolone acetonide at 10 to 10 mol/L decreased human tenocyte viability to 45% to 88% of control in a dose-dependent manner. Cell proliferation was suppressed to 87% +/- 8% at all doses. Treatment with 1 micromol/L triamcinolone acetonide reduced the amount of collagen synthesis as measured by H-proline incorporation from 40 +/- 2 cpm/1000 cells to 27 +/- 4 cpm/1000 cells. The suppressed human tenocyte cellular activity and reduced collagen production may lead to disturbed tendon structure and predispose the tendon to subsequent spontaneous rupture.