Nicotine reduced MMP‐9 expression in the primary porcine tenocytes exposed to cyclic stretch

Nicotine is one of the major chemical components of the cigarette smoke, which has been known as a risk factor for tendon ruptures including rotator cuff tears. This study investigated the effect of nicotine on tenocytes under cyclic‐stretched condition. Particularly, we focused on the morphologic changes of tenocytes and their expression of MMPs. Primary porcine tenocytes were obtained from the infraspinatus tendon. The cells were cultured on elastic chambers under static or cyclic‐stretched condition for 24 h in the existence of nicotine (0, 1, 10, and 100 µM). Cell shape, gene expression of collagen type I and III, MMPs (‐1, ‐2, ‐3, ‐9, and ‐13) and TIMPs (‐1, ‐2, and ‐3) and enzyme activity of MMP‐9 were analyzed using immunohistochemistry, RT‐PCR, and zymography. Tenocytes exposed to nicotine represented significantly decreased gene expressions in MMP‐9 (p < 0.001) and TIMP‐3 (p < 0.05) under the cyclic stretch. Enzymatic activity of MMP‐9 was also reduced by nicotine exposure in a dose‐dependent manner (p < 0.001). The down‐regulation of MMP and TIMP expression by nicotine shown in our in vitro experiment might deteriorate normal metabolism of the tendon. These mechanisms might affect the mechanical properties of the extracellular matrix of the rotator cuff tendon. © 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 31: 645–650, 2013     

Dose–response effect of an intra‐tendon application of recombinant human platelet‐derived growth factor‐BB (rhPDGF‐BB) in a rat Achilles tendinopathy model

The purpose of this study was to assess whether intra‐tendon delivery of recombinant human platelet‐derived growth factor‐BB (rhPDGF‐BB) would improve Achilles tendon repair in a rat collagenase‐induced tendinopathy model. Seven days following collagenase induction of tendinopathy, one of four intra‐tendinous treatments was administered: (i) Vehicle control (sodium acetate buffer), (ii) 1.02 µg rhPDGF‐BB, (iii) 10.2 µg rhPDGF‐BB, or (iv) 102 µg rhPDGF‐BB. Treated tendons were assessed for histopathological (e.g., proliferation, tendon thickness, collagen fiber density/orientation) and biomechanical (e.g., maximum load‐to‐failure and stiffness) outcomes. By 7 days post‐treatment, there was a significant increase in cell proliferation with the 10.2 and 102 µg rhPDGF‐BB‐treated groups (p = 0.049 and 0.015, respectively) and in thickness at the tendon midsubstance in the 10.2 µg of rhPDGF‐BB group (p = 0.005), compared to controls. All groups had equivalent outcomes by Day 21. There was a dose‐dependent effect on the maximum load‐to‐failure, with no significant difference in the 1.02 and 102 µg rhPDGF‐BB doses but the 10.2 µg rhPDGF‐BB group had a significant increase in load‐to‐failure at 7 (p = 0.003) and 21 days (p = 0.019) compared to controls. The rhPDGF‐BB treatment resulted in a dose‐dependent, transient increase in cell proliferation and sustained improvement in biomechanical properties in a rat Achilles tendinopathy model, demonstrating the potential of rhPDGF‐BB treatment in a tendinopathy application. Consequently, in this model, data suggest that rhPDGF‐BB treatment is an effective therapy and thus, may be an option for clinical applications to treat tendinopathy. © 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 31: 413–420, 2013     

New surgical model of post‐traumatic osteoarthritis: Isolated intra‐articular bone injury in the rabbit

Osteoarthritis (OA) is a leading cause of disability worldwide. We hypothesized that inflammation following isolated intra‐articular bone injury can stimulate post‐traumatic OA and developed a rabbit model to test that concept. Sixty female New Zealand White Rabbits were used. Twenty‐six experimental animals had two holes drilled into their right femoral‐notch, 18 rabbits had sham surgery, and 16 were un‐operated controls. Rabbits were euthanized in subgroups at 72 h, 3, 6, 9, and 52 weeks. Knees were assessed grossly and tissues collected. Cartilage and synovium were analyzed with histology and qPCR and subgroups compared statistically. All surgical joints showed gross and histological (modified Mankin score) cartilage damage after surgery, with experimentals worsening with time (p < 0.05). Cartilage qPCR showed fivefold increases in TGFβ (p < 0.05) expression at 72 h and 3 weeks with sixfold increases in MMP13 (p < 0.025) expression at 72 h. By 6 weeks, expression of these markers was similar to baseline levels. Synovial membrane thickening with increased cellularity was seen at both 9 and 52 weeks (p < 0.05). Short‐term synovial inflammatory marker (IL‐1β, IL‐Ra, IL‐6, and IL‐8) expression was three‐ to fourfold increase in experimentals at 72 h (p < 0.01) returning to baseline levels by 3 weeks. Intra‐articular bone injury creates early joint inflammation with some chronic synovial changes and progressive cartilage damage consistent with OA in adult rabbits. This model provides an exciting new avenue to potentially explore some relevant inflammatory drivers of OA without major mechanical variables. © 2013 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 31: 914–920, 2013     

Expression of matrix metalloproteinases 1, 3, and 9 in degenerated long head biceps tendon in the presence of rotator cuff tears: an immunohistological study

Background  

Long head biceps (LHB) degeneration, in combination with rotator cuff tears, can be a source of chronic shoulder pain. LHB tenotomy reduces pain and improves joint function although the pathophysiological context is not well understood. Tendon integrity depends on the extracellular matrix (ECM), which is regulated by matrix metalloproteinases (MMP). It is unclear which of these enzymes contribute to LHB but we chose to study MMP 1, 3, and 9 and hypothesized that one or more of them may be altered in LHB, whether diagnosed preoperatively or intraoperatively. We compared expression of these MMPs in both LHB and healthy tendon samples.     

The tendon of the long head of the biceps in complex proximal humerus fractures: A histological perspective

We have studied the histologic and immunohistochemical changes of the long head of the biceps brachii tendon (LHB) in low-energy complex proximal humerus fractures. Our objective was to detect histological features, which may be correlated to pain generation.Biopsy samples were obtained during hemiarthroplasty procedures from 11 patients who suffered a complex proximal humerus fracture. The control group consisted of 10 samples harvested from human cadavers with no history of premortem shoulder problems and no gross shoulder pathology. Histologic investigation included quantitative measurement of tendon degeneration, cellularity, neoangiogenesis, inflammation and metaplasia, as well as immunohistochemical detection of cells with neural differentiation within the tendon tissue proper with S-100 protein and neuropeptide Y (N-Y).The found lesions were significantly more in the group of tendons from fractures compared to the control group (p < 0.001). These lesions were also statistically correlated to each other, indicating a possible neural differentiation of tendon stromal cells.The LHB is a potential source of pain and the routine use of tenotomy/tenodesis of this tendon in hemiarthroplasty procedures for fracture may be reinforced by the results of this study.     

Use of an IL1‐receptor antagonist to prevent the progression of tendinopathy in a rat model

This study evaluated if inhibiting IL1‐β activity with an IL1‐receptor antagonist (IL1‐RA) will prevent pathologic changes commonly seen in tendinopathy. Thirty‐six Sprague–Dawley retired‐breeder rats were divided into three groups having weekly bilateral patellar tendon injections: CON (0.1 ml Saline), CAR (0.1 ml 2% carrageenan), IL1‐RA (0.1 ml 2% CAR plus 0.94 mg of the IL1‐RA, 2.5 mg/kg). Carrageenan was used to establish tendinopathy in two groups due to its ability to develop tendinopathy in prior studies. Animals were euthanized 3 weeks after initial injection. The CAR group demonstrated significantly (p < 0.05) shorter tendon lengths (8.61 ± 0.38 mm) relative to CON (8.94 ± 0.38 mm) that was prevented in the IL1‐RA (9.02 ± 0.30 mm) as well as significantly increased collagenase activity in the CAR (0.061 ± 0.043) compared to CON (0.027 ± 0.015) (p< 0.05). By histological evaluation, the CAR group demonstrated significantly greater inflammation than IL1‐RA, and CON (p < 0.05). CAR showed a trend for increased cross‐sectional area relative to CON that was absent in the IL1‐RA. IL1‐RA can effectively inhibit the development of mechanical, chemical, and histologic changes seen with carrageenan‐induced tendonitis. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:616–622, 2016.     

Biceps tenodesis versus biceps tenotomy for biceps tendinitis without rotator cuff tears

Disorders of the long head of the biceps tendon (LHB) are a well-recognised cause of shoulder pain despite the function of the long head of the biceps remaining poorly understood. There has been a dramatic rise in the number of biceps tenodesis procedures being performed in the last decade. This may partly be attributed to concerns regarding residual cosmetic deformity and pain after biceps tenotomy though there is little evidence to suggest that functional outcomes of tenodesis are superior to biceps tenotomy. Current literature focuses on LHB disorders with concomitant rotator cuff tears. The aim of this review is to discuss the anatomy of the LHB, the pathogenesis of tendinopathy of the LHB, indications of biceps tenodesis and tenotomy and compare the current literature on the functional outcomes of these procedures for LHB disorders in the absence of rotator cuff tears.     

Comparison of the effect of intra‐tendon applications of recombinant human platelet‐derived growth factor‐BB,platelet‐rich plasma,steroids in a rat achilles tendon collagenase model

This study compared the effect of intra‐tendon (IT) delivery of recombinant human platelet‐derived growth factor‐BB (rhPDGF‐BB), platelet‐rich plasma (PRP) and corticosteroids in a rat tendinopathy model. Seven days after collagenase induction of tendinopathy, a 30‐µl IT injection was administered. Treatments included: saline; 3 µg rhPDGF‐BB; 10 µg rhPDGF‐BB; PRP; and 300 µg triamcinolone acetonide (TCA). Outcomes were assessed 7 and 21 days after treatment. All groups exhibited good to excellent repair. Relative to saline, cell proliferation increased 65% in the 10 µg rhPDGF‐BB group and decreased 74% in the TCA group; inflammation decreased 65% in the TCA group. At 7 days, maximum load‐to‐failure was increased in the 3 µg rhPDGF‐BB group relative to saline, PRP, and TCA (p < 0.025). On day 21, maximum load‐to‐rupture was increased in the 10 µg rhPDGF‐BB group relative to saline, PRP, and TCA (p < 0.035) and in the 3 µg rhPDGF‐BB group compared to saline and TCA (p < 0.027). Stiffness in the 10 µg rhPDGF‐BB group was increased compared to saline, PRP, and TCA (p < 0.038). Histology demonstrated similar repair in all groups. PRP and TCA did not improve mechanical properties compared to saline. Injections of rhPDGF‐BB increased maximum load‐to‐failure (3 and 10 µg) and stiffness (10 µg) relative to controls and commonly used treatments. © 2013 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 32:145–150, 2014.     

A functional polymorphism in MMP1 could influence osteomyelitis development

Osteomyelitis (OM) is a bone infection characterized by necrosis and new formation of bone. Because matrix metalloproteases (MMPs) play an important role in bone extracellular matrix remodeling, we investigated the role of some MMP polymorphisms in OM patients. A total of 118 OM patients and 300 blood donors were genotyped for the polymorphisms of MMP1 (?1607 1G/2G) and MMP13 (?77A/G). Levels of MMPs (?1, ?2, ?3, ?8, ‐9, ?10, and ?13) and tissue inhibitors of metaloproteases (TIMP‐1, ‐2, and ‐4) in serum and in human osteoblasts obtained from OM biopsies also were determined. The MMP1 (–1607 2G/2G) genotype was significantly more frequent among OM patients compared with controls [65.3% versus 33.7%, χ² = 26.85, odds ratio (OR) = 3.24, 95% confidence interval (CI) 2.03–5.2, p < .0001]. The MMP1 2G allele also was more frequent in OM patients (73.3% versus 57.2%, χ² = 37.76, OR = 2.75, 95% CI 1.96–3.85, p < .0001). Carriers of the 2G allele had significantly higher osteoblast MMP1 mRNA and MMP‐1 serum levels than noncarriers (p < .04). Interleukin 1α (IL‐1α) increased MMP‐1 and ‐13 protein secretion and Ets1 mRNA expression by OM patients' osteoblasts. No association of the MMP13 (–77 A/G) polymorphism with OM was observed. The MMP1 (–1607 1G/2G) polymorphism might contribute to OM pathogenesis. This could be due to increased expression of MMP‐1 by osteoblasts and is regulated by IL‐1α. © 2010 American Society for Bone and Mineral Research     

Mesenchymal stem cells and insulin‐like growth factor‐I gene‐enhanced mesenchymal stem cells improve structural aspects of healing in equine flexor digitorum superficialis tendons

Tendinitis remains a catastrophic injury among athletes. Mesenchymal stem cells (MSCs) have recently been investigated for use in the treatment of tendinitis. Previous work has demonstrated the value of insulin‐like growth factor‐I (IGF‐I) to stimulate cellular proliferation and tendon fiber deposition in the core lesion of tendinitis. This study examined the effects of MSCs, as well as IGF‐I gene‐enhanced MSCs (AdIGF‐MSCs) on tendon healing in vivo. Collagenase‐induced bilateral tendinitis lesions were created in equine flexor digitorum superficialis tendons (SDFT). Tendons were treated with 10 × 10⁶ MSCs or 10 × 10⁶ AdIGF‐MSCs. Control limbs were injected with 1 mL of phosphate‐buffered saline (PBS). Ultrasound examinations were performed at t = 0, 2, 4, 6, and 8 weeks. Horses were euthanized at 8 weeks and SDFTs were mechanically tested to failure and evaluated for biochemical composition and histologic characteristics. Expression of collagen types I and III, IGF‐I, cartilage oligomeric matrix protein (COMP), matrix metalloproteinase‐3 (MMP‐3), matrix metalloproteinase‐13 (MMP‐13), and aggrecanase‐1 (ADAMTS‐4) were similar in MSC and control tendons. Both MSC and AdIGF‐MSC injection resulted in significantly improved tendon histological scores. These findings indicate a benefit to the use of MSCs and AdIGF‐MSCs for the treatment of tendinitis. © 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 27:1392–1398, 2009     

Multiple injections of leukoreduced platelet rich plasma reduce pain and functional impairment in a canine model of ACL and meniscal deficiency

Platelet rich plasma (PRP) is used to treat many musculoskeletal disorders. We used a canine model to determine the effects of multiple intra‐articular injections of leukoreduced PRP (ACP) on anterior cruciate ligament healing, meniscal healing, and progression of osteoarthritis (OA). With Animal Care and Use Committee (ACUC) approval, 12 dogs underwent partial ACL transection and meniscal release in one knee. At weeks 1, 2, 3, 6, and 8 after insult, dogs were treated with intra‐articular injections (2 ml) of either ACP (n = 6) or saline (n = 6). Dogs were assessed over 6 months to determine comfortable range of motion (CROM), lameness, pain, effusion, kinetics, and radiographic and arthroscopic assessments. At 6‐month endpoint, dogs were assessed for ACL material properties and histopathology. Saline‐treated dogs had significantly (p < 0.04) more CROM loss, significantly (p < 0.01) more pain, significantly (p < 0.05) more severe lameness, significantly (p < 0.05) lower function, and significantly (p < 0.05) lower %Total Pressure Index in affected hindlimbs compared to ACP‐treated dogs. Radiographic OA increased significantly (p < 0.01) over time within each group. Arthroscopically, saline‐treated knees showed moderate to severe synovitis, further ACL disruption, and medial compartment cartilage loss, and ACP‐treated knees showed evidence of ACL repair and less severe synovitis. ACL material properties in ACP‐treated knees were closer to normal than in saline‐treated knees, however, the differences were not statistically significant. ACL histopathology was significantly (p< 0.05) less severe in ACP‐treated knees compared to saline‐treated knees. Five intra‐articular injections of leukoreduced PRP had beneficial effects for ACL healing, improved range of motion, decreased pain, and improved limb function for up to 6 months in this model. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:607–615, 2016.     

Insulin Resistance and the IGF‐I‐Cortical Bone Relationship in Children Ages 9 to 13 Years

IGF‐I is a pivotal hormone in pediatric musculoskeletal development. Although recent data suggest that the role of IGF‐I in total body lean mass and total body bone mass accrual may be compromised in children with insulin resistance, cortical bone geometric outcomes have not been studied in this context. Therefore, we explored the influence of insulin resistance on the relationship between IGF‐I and cortical bone in children. A secondary aim was to examine the influence of insulin resistance on the lean mass‐dependent relationship between IGF‐I and cortical bone. Children were otherwise healthy, early adolescent black and white boys and girls (ages 9 to 13 years) and were classified as having high (n = 147) or normal (n = 168) insulin resistance based on the homeostasis model assessment of insulin resistance (HOMA‐IR). Cortical bone at the tibia diaphysis (66% site) and total body fat‐free soft tissue mass (FFST) were measured by peripheral quantitative computed tomography (pQCT) and dual‐energy X‐ray absorptiometry (DXA), respectively. IGF‐I, insulin, and glucose were measured in fasting sera and HOMA‐IR was calculated. Children with high HOMA‐IR had greater unadjusted IGF‐I (p < 0.001). HOMA‐IR was a negative predictor of cortical bone mineral content, cortical bone area (Ct.Ar), and polar strength strain index (pSSI; all p ≤ 0.01) after adjusting for race, sex, age, maturation, fat mass, and FFST. IGF‐I was a positive predictor of most musculoskeletal endpoints (all p < 0.05) after adjusting for race, sex, age, and maturation. However, these relationships were moderated by HOMA‐IR (p_Interaction < 0.05). FFST positively correlated with most cortical bone outcomes (all p < 0.05). Path analyses demonstrated a positive relationship between IGF‐I and Ct.Ar via FFST in the total cohort (β_{Indirect Effect} = 0.321, p < 0.001). However, this relationship was moderated in the children with high (β_{Indirect Effect} = 0.200, p < 0.001) versus normal (β_{Indirect Effect} = 0.408, p < 0.001) HOMA‐IR. These data implicate insulin resistance as a potential suppressor of IGF‐I‐dependent cortical bone development, though prospective studies are needed. © 2017 American Society for Bone and Mineral Research.     

Age‐ and Sex‐Dependent Changes of Intra‐articular Cortical and Trabecular Bone Structure and the Effects of Rheumatoid Arthritis

The objective of this cross‐sectional study was to define normal sex‐ and age‐dependent values of intra‐articular bone mass and microstructures in the metacarpal heads of healthy individuals by high‐resolution peripheral quantitative computed tomography (HR‐pQCT) and test the effect of rheumatoid arthritis (RA) on these parameters. Human cadaveric metacarpal heads were used to exactly define intra‐articular bone. Healthy individuals of different sex and age categories and RA patients with similar age and sex distribution received HR‐pQCT scans of the second metacarpal head and the radius. Total, cortical, and trabecular bone densities as well as microstructural parameters were compared between 1) the different ages and sexes in healthy individuals; 2) between metacarpal heads and the radius; and 3) between healthy individuals and RA patients. The cadaveric study allowed exact definition of the intra‐articular (intracapsular) bone margins. These data were applied in measuring intra‐articular and radial bone parameters in 214 women and men (108 healthy individuals, 106 RA patients). Correlations between intra‐articular and radial bone parameters were good (r = 0.51 to 0.62, p < 0.001). In contrast to radial bone, intra‐articular bone remained stable until age 60 years (between 297 and 312 mg HA/cm³) but decreased significantly (p < 0.001) in women thereafter (237.5 ± 44.3) with loss of both cortical and trabecular bone. Similarly, RA patients showed significant (p < 0.001) loss of intra‐articular total (263.0 ± 44.8), trabecular (171.2 ± 35.6), and cortical bone (610.2 ± 62.0) compared with sex‐ and age‐adjusted controls. Standard sex‐ and age‐dependent values for physiological intra‐articular bone were defined. Postmenopausal state and RA led to significant decrease of intra‐articular bone. © 2016 American Society for Bone and Mineral Research.     

Tendon‐derived progenitor cells improve healing of collagenase‐induced flexor tendinitis

Tendinitis is a common and a performance‐limiting injury in athletes. This study describes the value of intralesional tendon‐derived progenitor cell (TDPC) injections in equine flexor tendinitis. Collagenase‐induced tendinitis was created in both front superficial digital flexor (SDF) tendons. Four weeks later, the forelimb tendon lesions were treated with 1 × 10⁷ autogenous TDPCs or saline. Tendinitis was also induced by collagenase in one hind SDF tendon, to study the survival and distribution of DiI‐labeled TDPCs 1, 2, 4, and 6 weeks after injection. The remaining normal tendon was used as a “control.” Twelve weeks after forelimb TDPC injections, tendons were harvested for assessment of matrix gene expression, biochemical, biomechanical, and histological characteristics. DiI‐labeled TDPCs were abundant 1 week after injection but gradually declined over time and were undetectable after 6 weeks. Twelve weeks after TDPC injection, collagens I and III, COMP and tenomodulin mRNA levels were similar (p = 0.3) in both TDPC and saline groups and higher (p < 0.05) than normal tendon. Yield and maximal stresses of the TDPC group were significantly greater (p = 0.005) than the saline group's and similar (p = 0.6) to normal tendon. However, the elastic modulus of the TDPC and saline groups were not significantly different (p = 0.32). Histological assessment of the repair tissues with Fourier transform‐second harmonic generation imaging demonstrated that collagen alignment was significantly better (p = 0.02) in TDPC group than in the saline controls. In summary, treating collagenase‐induced flexor tendon lesions with TDPCs improved the tensile strength and collagen fiber alignment of the repair tissue. Study Design © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:2162–2171, 2016.     

Genome‐wide analysis identifies differential promoter methylation of Leprel2, Foxf1, Mmp25, Igfbp6, and Peg12 in murine tendinopathy

We have used a murine Achilles tendinopathy model to investigate whether tissue changes (such as collagen disorganization, chondroid metaplasia, and loss of tensile properties) which are broadly characteristic of human tendinopathies, are accompanied by changes in the expression of chromatin‐modifying enzymes and the methylation status of promoter regions of tendon cell DNA. Tendinopathy was induced by two intra‐tendinous TGF‐β1 injections followed by cage activity or treadmill running for up to 28 days. Activation of DNA methyltransferases occurred at 3 days after the TGF‐β1 injections and also at 14 days, but only with treadmill activity. Genome‐wide Methyl Mini‐Seq™ analysis identified 19 genes with differentially methylated promoters, five of which perform functions with an apparent direct relevance to tendinopathy (Leprel2 , Foxf1 , Mmp25, Igfbp6 , and Peg12) . The functions of the genes identified included collagen fiber assembly and pericellular interactions, therefore their perturbation could play a role in the characteristic disorganization of fibers in affected tendons. We postulate that a study of the functional genomics of these genes in animal and human tendon could further delineate the pathogenesis of this multi‐factorial complex disease. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:947–955, 2017.

     

Cross-sectional area of the tendon and the muscle of the biceps brachii in shoulders with rotator cuff tears

Background The intraarticular portion of the long head of the biceps tendon is often widened in shoulders with cuff tears. It is unclear whether this is a local phenomen or is caused by muscle hypertrophy.

Methods We investigated morphological changes of the biceps brachii in 14 embalmed shoulders: 7 with intact rotator cuff and 7 with rotator cuff tears.

We measured the cross-sectional area (CSA) of the tendon of the long head of the biceps (LHB) at 9 levels between the glenoid origin and the musculotendinous junction. The muscle volume and the muscle fiber length of the long and short heads of the biceps were measured to calculate the physiological CSA (PCSA) by dividing the volume by the fiber length.

Results The CSA of the LHB tendon at the entrance to the bicipital groove was greater in cuff tear shoulders than in normal shoulders. The PCSA of the biceps was similar in normal and cuff tear shoulders.

Interpretation Hypertrophy of the LHB tendon appears to be a localized morphological change near the entrance to the bicipital groove.     

MMP‐1 promoter polymorphism is associated with primary tendinopathy of the posterior tibial tendon

Posterior tibial tendon (PTT) dysfunction is recognized as an etiology leading to acquired flatfoot in adults, causing significant functional loss. Many risk factors and systemic conditions have been proposed in literature. However, many patients present PTT dysfunction without any of these characteristics. This suggests that there could be a genetic influence associated with posterior tibial tendinopathy. The purpose of the present study is to investigate the association of the ?1607 polymorphism in the promoter gene of MMP‐1 and posterior tibial tendinopathy. The test group included 50 women, who presented PTT dysfunction grade 2 or 3, and who were submitted to surgical treatment, with histopathological examination of the tendon and magnetic resonance image (MRI) confirming tendinopathy, while the control group was 100 asymptomatic women who presented intact PTT at MRI. The results were analyzed using the chi‐square test. The data showed a 75% incidence of the allele 1G and 62% of the genotype 1G/1G at the control group while, at the test group, they showed a 78% incidence of the allele 2G and 72% of the genotype 2G/2G (p < 0.001). The ?1607 polymorphism of promoter gene of MMP‐1 is associated with the posterior tibial tendinopathy in the studied population. © 2013 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 31:1103–1107, 2013