Osteonecrosis is a phenomenon involving disruption to the vascular supply to the femoral head, resulting in articular surface collapse and eventual osteoarthritis. Although alcoholism, steroid use, and hip trauma remain the most common causes, several other etiologies for osteonecrosis have been identified. Basic science research utilizing animal models and stem cell applications continue to further elucidate the pathophysiology of osteonecrosis and promise novel treatment options in the future. Clinical studies evaluating modern joint-sparing procedures have demonstrated significant improvements in outcomes, but hip arthroplasty is still the most common procedure performed in these affected younger adults. Further advances in joint-preserving procedures are required and will be widely studied in the coming decade.
SUMMARY
Primary cilia are found on nearly every mammalian cell, including osteocytes, fibroblasts, and chondrocytes. However, the functions of primary cilia have not been extensively studied in these cells, particularly chondrocytes. Interestingly, defects in the primary cilium result in skeletal defects such as polydactyly in Bardet-Biedl Syndrome (BBS), a ciliary disorder that also results in obesity, retinopathy, and cognitive impairments (1–4). Wild-type mice and mutant mice of the ciliary proteins Bbs1, Bbs2, and Bbs6 were evaluated with respect to histological and biochemical differences in chondrocytes from articular cartilage and xiphoid processes. Using immunofluorescence microscopy, chondrocytic cilia were visualized from the load-bearing joints and non-load-bearing xiphoid processes. Significant differences in ciliary morphology were not identified between mutant and wild-type mice. However, after expanding chondrocytes in cell culture and implanting them in solid agarose matrix, it was seen that the fraction of ciliated cells in cultures from mutant mice was significantly lower than in the wild-type cultures (p<.05). In addition, in Safranin-O-stained whole joint sections, Bbs mutant mice had significantly lower articular joint thickness (p<.05) and lower proteoglycan content saturation (p<.05) than wild-type mice. Moreover, there were statistically significant differences of cell distribution between Bbs mutant and wild-type mice (p<.05), indicating that mutant articular cartilage had changes consistent with early signs of osteoarthritis. These data indicate that Bbs genes and their functions in the chondrocytic primary cilium are important for normal articular cartilage maintenance.
The CyberGlove II can be utilized in the dynamic functional analysis of the hand and is able to detect a triggering event in subjects with known stenosing tenosynovitis. Those subjects demonstrate a significant decrease in maximum velocity in slow fist tasks, highlighting the need for comprehensive assessment to ascertain the full extent of functional limitations that can occur in the setting of hand pathology.
Our studies suggest that MSC mobilization through S1PR3 antagonism is a promising strategy for endogenous tissue engineering and improving MSC delivery to treat bone diseases.
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