Knockout of hyaluronan synthase 1, but not 3, impairs formation of the retrocalcaneal bursa.

Hyaluronan (HA), a high molecular weight non-sulfated glycosaminoglycan, is an integral component of the extracellular matrix of developing and mature connective tissues including tendon. There are few published reports quantifying HA content during tendon growth and maturation, or detailing its effects on the mechanical properties of the tendon extracellular matrix. Therefore, the goal of the current study was to examine the role of HA synthesis during post-natal skeletal growth and maturation, and its influence on tendon structure and biomechanical function. For this purpose, the morphological, biochemical, and mechanical properties of Achilles tendons from wild type (WT) and hyaluronan synthase 1 and 3 deficient mouse strains (Has1-/- (Has1KO), Has3-/- (Has3KO), and Has1-/- 3-/- (Has1/3KO)) were determined at 4, 8, and 12 weeks of age. Overall, HAS-deficient mice did not show any marked differences from WT mice in Achilles tendon morphology or in the HA and chondroitin/dermatan sulfate (CS/DS) contents. However, HAS1-deficiency (in the single or Has1/3 double KO) impeded post-natal formation of the retrocalcaneal bursa, implicating HAS1 in regulating HA metabolism by cells lining the bursal cavity. Together, these data suggest that HA metabolism via HAS1 and HAS3 does not markedly influence the extracellular matrix structure or function of the tendon body, but plays a role in the formation/maintenance of peritendinous bursa. Additional studies are warranted to elucidate the relationship of HA and CS/DS metabolism to tendon healing and repair in vivo. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:2622-2632, 2018.

Proinflammatory cytokines and metalloproteases are expressed in the subacromial bursa in patients with rotator cuff disease.

PURPOSE: The pathophysiology of subacromial impingement syndrome is poorly understood. We investigated the expression of inflammatory cytokines, metalloproteases, and the cyclooxygenases in the subacromial bursa in control patients and in patients with rotator cuff tear. TYPE OF STUDY: Basic science evaluation. METHODS: Eighteen patients undergoing shoulder surgery had a subacromial bursa biopsy examination. Patients were divided into 2 groups. Group I (study group) had 10 patients with a full-thickness rotator cuff tear (RCT). Group II (control group) had 8 patients. Seven of 8 underwent shoulder arthroscopy with anterior capsular reconstruction for instability; 1 of 8 underwent open reduction internal fixation for acute proximal humerus fracture. None of the patients in group II had any history of symptoms or signs consistent with subacromial impingement. H&E and immunohistochemical antibody (MMP-1, MMP-9, IL-1, IL-6, TNF-alpha, COX-1, and COX-2) stained specimens were examined by 2 blinded observers using a histologic scale (grade 0 = no staining to grade 4 = intense staining). RESULTS: Histologic evidence of inflammation was present in all patients with RCT (group I). No or mild inflammation was noted in group II. The average staining grade for inflammatory cytokines (IL-1, IL-6, TNF-alpha) and proteinases (MMP-1 and MMP-9) was significantly more pronounced in the RCT group (P < .001). Cyclooxygenase enzymes (COX-1 and COX-2) were also increased in group II (P < .001). CONCLUSIONS: A high level of expression of inflammatory cytokines, proteinases, and cyclooxygenase enzymes, known to produce a catabolic environment, is present in the subacromial bursa of patients with rotator cuff tear. CLINICAL RELEVANCE: These findings support the role of nonsteroidal anti-inflammatory drugs and corticosteroids in RCT treatment, and emphasize the importance of subacromial bursectomy to reduce inflammation in RCT surgery.