Gene expression and matrix turnover in overused and damaged tendons

Chronic, painful conditions affecting tendons, frequently known as tendinopathy, are very common types of sporting injury. The tendon extracellular matrix is substantially altered in tendinopathy, and these changes are thought to precede and underlie the clinical condition. The tendon cell response to repeated minor injuries or “overuse” is thought to be a major factor in the development of tendinopathy. Changes in matrix turnover may also be effected by the cellular response to physical load, altering the balance of matrix turnover and changing the structure and composition of the tendon. Matrix turnover is relatively high in tendons exposed to high mechanical demands, such as the supraspinatus and Achilles, and this is thought to represent either a repair or tissue maintenance function. Metalloproteinases are a large family of enzymes capable of degrading all of the tendon matrix components, and these are thought to play a major role in the degradation of matrix during development, adaptation and repair. It is proposed that some metalloproteinase enzymes are required for the health of the tendon, and others may be damaging, leading to degeneration of the tissue. Further research is required to investigate how these enzyme activities are regulated in tendon and altered in tendinopathy. A profile of all the metalloproteinases expressed and active in healthy and degenerate tendon is required and may lead to the development of new drug therapies for these common and debilitating sports injuries

Expression profiling of metalloproteinases and tissue inhibitors of metalloproteinases in normal and degenerate human achilles tendon

To profile the messenger RNA (mRNA) expression for the 23 known genes of matrix metalloproteinases (MMPs), 19 genes of ADAMTS, 4 genes of tissue inhibitors of metalloproteinases (TIMPs), and ADAM genes 8, 10, 12, and 17 in normal, painful, and ruptured Achilles tendons. Tendon samples were obtained from cadavers or from patients undergoing surgical procedures to treat chronic painful tendinopathy or ruptured tendon. Total RNA was extracted and mRNA expression was analyzed by quantitative real-time reverse transcription–polymerase chain reaction, normalized to 18S ribosomal RNA. In comparing expression of all genes, the normal, painful, and ruptured Achilles tendon groups each had a distinct mRNA expression signature. Three mRNA were not detected and 14 showed no significant difference in expression levels between the groups. Statistically significant (P < 0.05) differences in mRNA expression, when adjusted for age, included lower levels of MMPs 3 and 10 and TIMP-3 and higher levels of ADAM-12 and MMP-23 in painful compared with normal tendons, and lower levels of MMPs 3 and 7 and TIMPs 2, 3, and 4 and higher levels of ADAMs 8 and 12, MMPs 1, 9, 19, and 25, and TIMP-1 in ruptured compared with normal tendons. The distinct mRNA profile of each tendon group suggests differences in extracellular proteolytic activity, which would affect the production and remodeling of the tendon extracellular matrix. Some proteolytic activities are implicated in the maintenance of normal tendon, while chronically painful tendons and ruptured tendons are shown to be distinct groups. These data will provide a foundation for further study of the role and activity of many of these enzymes that underlie the pathologic processes in the tendon

Mid-portion Achilles tendinopathy: why painful? An evidence-based philosophy

Chronic mid-portion Achilles tendinopathy is generally difficult to treat as the background to the pain mechanisms has not yet been clarified. A wide range of conservative and surgical treatment options are available. Most address intratendinous degenerative changes when present, as it is believed that these changes are responsible for the symptoms. Since up to 34% of asymptomatic tendons show histopathological changes, we believe that the tendon proper is not the cause of pain in the majority of patients. Chronic painful tendons show the ingrowth of sensory and sympathetic nerves from the paratenon with release of nociceptive substances. Denervating the Achilles tendon by release of the paratenon is sufficient to cause pain relief in the majority of patients. This type of treatment has the additional advantage that it is associated with a shorter recovery time when compared with treatment options that address the tendon itself. An evidence-based philosophy on the cause of pain in chronic mid-portion Achilles tendinopathy is presented

Hip Fracture Incidence in Relation to Age, Menopausal Status, and Age at Menopause: Prospective Analysis

Using data from the UK Million Women Study, Emily Banks and colleagues investigate the relationships between the incidence of hip fracture and a woman's age, menopausal status, and age at menopause

Study protocol for prevention of falls: A randomized controlled trial of effects of vitamin D and exercise on falls prevention

Peer reviewe

Surgical treatment for chronic Achilles tendinopathy: a prospective seven month follow up study

Objective: To prospectively assess the early results of surgical treatment of chronic Achilles tendinopathy. Methods: This seven month prospective follow up study assessed the short term results of surgical treatment of chronic Achilles tendinopathy and compared the subjective and functional outcome of patients with Achilles tendinopathy without a local intratendinous lesion (group A) with that of similar patients with such a lesion (group B). Forty two of the initial 50 patients were examined before surgery and after the seven month follow up. Evaluation included an interview, subjective evaluation, clinical tests, and a performance test. Results: At the follow up, physical activity was fully restored in 28 of the 42 patients (67%), and 35 patients (83%) were asymptomatic or had only mild pain during strenuous exercise. In clinical tests, significant improvements were observed in climbing up and down stairs and the rising on the toes test. Surgical treatment also seemed to be successful from the total test score, which was excellent or good in 35 patients, compared with before surgery when it was excellent or good in one patient only. Patients in group A fared better than those in group B, whether evaluated by recovery of physical activity after surgery (88% v 54%) or the complication rate (6% v 27%). Conclusions: Surgical treatment of chronic Achilles tendinopathy gives good and acceptable short term results. A lower complication rate and a trend to better recovery was observed in patients with peritendinous adhesions only than in those with peritendinous adhesions combined with an intratendinous lesion

Trends in the surgical treatment of proximal humeral fractures – a nationwide 23-year study in Finland

<p>Abstract</p> <p>Background</p> <p>Proximal humeral fractures are common osteoporotic fractures. Most proximal humeral fractures are treated non-surgically, although surgical treatment has gained popularity. The purpose of this study was to determine changes in the surgical treatment of proximal humeral fractures in Finland between 1987 and 2009.</p> <p>Methods</p> <p>The study covered the entire adult (>19 y) population in Finland over the 23-year period from 1st of January 1987 to 31st of December 2009. We assessed the number and incidence of surgically treated proximal humeral fractures in each year of observation and recorded the type of surgery used. The cohort study was based on data from Finnish National Hospital Discharge Register.</p> <p>Results</p> <p>During the 23-year study period, a total of 10,560 surgical operations for proximal humeral fractures were performed in Finland. The overall incidence of these operations nearly quadrupled between 1987 and 2009. After the year 2002, the number of patients treated with plating increased.</p> <p>Conclusion</p> <p>An increase in the incidence of the surgical treatment of proximal humeral fractures was seen in Finland in 1987–2009. Fracture plating became increasingly popular since 2002. As optimal indications for each surgical treatment modality in the treatment of proximal humeral fractures are not known, critical evaluation of each individual treatment method is needed.</p