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Emerging evidence suggests that connexin mediated gap junctional intercellular communication contributes to many aspects of bone biology including bone development, maintenance of bone homeostasis and responsiveness of bone cells to diverse extracellular signals. Deletion of connexin 43, the predominant gap junction protein in bone, is embryonic lethal making it challenging to examine the role of connexin 43 in bone in vivo. However, transgenic murine models in which only osteocytes and osteoblasts are deficient in connexin 43, and which are fully viable, have recently been developed. Unfortunately, the bone phenotype of different connexin 43 deficient models has been variable. To address this issue, we used an osteocalcin driven Cre-lox system to create osteoblast and osteocyte specific connexin 43 deficient mice. These mice displayed bone loss as a result of increased bone resorption and osteoclastogenesis. The mechanism underlying this increased osteoclastogenesis included increases in the osteocytic, but not osteoblastic, RANKL/OPG ratio. Previous in vitro studies suggest that connexin 43 deficient bone cells are less responsive to biomechanical signals. Interestingly, and in contrast to in vitro studies, we found that connexin 43 deficient mice displayed an enhanced anabolic response to mechanical load. Our results suggest that transient inhibition of connexin 43 expression and gap junctional intercellular communication may prove a potentially powerful means of enhancing the anabolic response of bone to mechanical loading.

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To determine the influence of rotator cuff muscle activity on humeral head migration relative to the glenoid during active arm elevation we studied five fresh cadaveric shoulders. The shoulder girdles were mounted in an apparatus that simulated contraction of the deltoid and rotator cuff muscles while maintaining the normal scapulothoracic relationship. The arms were abducted using four different configurations of simulated muscle activity: deltoid alone; deltoid and supraspinatus; deltoid, infraspinatus, teres minor, and subscapularis; and deltoid, supraspinatus, infraspinatus, teres minor, and subscapularis. For each simulated muscle configuration the vertical position of the humeral head in relation to the glenoid was determined at 30 degrees, 60 degrees, 90 degrees, and 120 degrees of abduction using digitized anteroposterior radiographs. Both muscle activity and abduction angle significantly influenced the glenohumeral relationship. With simulated activity of the entire rotator cuff, the geometric center of the humeral head was centered in the glenoid at 30 degrees but had moved 1.5 mm superiorly by 120 degrees. Abduction without the subscapularis, infraspinatus, and teres minor muscles caused significant superiorly directed shifts in humeral head position as did abduction using only the deltoid muscle. These results support the possible use of selective strengthening exercises for the infraspinatus, teres minor, and subscapularis muscles in treatment of the impingement syndrome.