Extracellular matrix with the rigidity of adipose tissue helps 3T3-L1 adipocytes maintain insulin responsiveness

Despite the popularity of 3T3-L1 adipocytes as a model system of adipocytes in vivo, they do not carry all of the cellular functions of adipocytes in vivo. In this study, we investigated the effect of extracellular matrix (ECM) rigidity on insulin signal transduction in 3T3-L1 adipocytes. On 250 Pa polyacrylamide gel (soft gel) laminated with a mixture of collagen type 1 and fibronectin, whose rigidity matches that of adipose tissue, expression of the insulin receptor, IRS-1 and AKT was upregulated and their insulin-stimulated phosphorylation was enhanced. Furthermore, the expression of GLUT1 was downregulated, whereas the expression of GLUT4 was unaffected as ECM rigidity decreased. Insulin-stimulated GLUT4 recruitment to the plasma membrane was significantly enhanced in cells seeded on soft gel. These results suggest that adjusting the ECM rigidity to that of adipose tissue augments insulin signaling in 3T3-L1 adipocytes and enhances insulin-stimulated GLUT4 recruitment to the plasma membrane

The mycobacterial desaturase DesA2 is associated with mycolic acid biosynthesis

Mycolic acids are critical for the survival and virulence of Mycobacterium tuberculosis, the causative agent of tuberculosis. Double bond formation in the merochain of mycolic acids remains poorly understood, though we have previously shown desA1, encoding an aerobic desaturase, is involved in mycolic acid desaturation. Here we show that a second desaturase encoded by desA2 is also involved in mycolate biosynthesis. DesA2 is essential for growth of the fast-growing Mycobacterium smegmatis in laboratory media. Conditional depletion of DesA2 led to a decrease in mycolic acid biosynthesis and loss of mycobacterial viability. Additionally, DesA2-depleted cells also accumulated fatty acids of chain lengths C19-C24. The complete loss of mycolate biosynthesis following DesA2 depletion, and the absence of any monoenoic derivatives (found to accumulate on depletion of DesA1) suggests an early role for DesA2 in the mycolic acid biosynthesis machinery, highlighting its potential as a drug target

Impact of combining medial capsule interposition with modified scarf osteotomy for hallux valgus

Objectives: To clarify the effect of combining medial capsule interposition with modified scarf osteotomy for hallux valgus. Methods: A multicenter, retrospective study included 64 cases [59 osteoarthritis patients (excluding rheumatoid arthritis); age 68.8 years, range 40–93 years] of modified scarf osteotomy which were performed from 2013 to 2017 and followed for 26.6 (range, 13–50) months. Patients were treated by either (1) without medial capsule interposition (33 cases) or (2) combined with interposition (31 cases) at each senior surgeon’s discretion. The Japanese Society for Surgery of the Foot (JSSF) hallux metatarsophalangeal (MTP)-interphalangeal scale was evaluated along with radiographic parameters (hallux valgus angle [HVA], first and second metatarsals intermetatarsal angles, and Hardy grade). Results: All JSSF scale and radiographic parameters were similar at baseline and significantly improved at final follow-up in both groups (pre-operation vs. final follow-up: p <.001). However, compared to without interposition group, interposition group showed significantly higher improvement in the JSSF scale (pre-operation to final follow-up: p value between the two groups at final follow-up) for pain (without interposition: 19.4–34.2, interposition: 18.4–37.1; p =.02), function (without interposition: 20.8–33.6, interposition: 18.3–36.6; p =.005), total score (without interposition: 41.5–81.8, interposition: 38.5–88.5; p <.001), and the MTP joint space (without interposition: 1.4–1.5 mm, interposition: 1.6–2.6 mm; p <.001) with significant correlation between the total JSSF score (r =.40; p =.001). Conclusion: Combining medial capsule interposition with modified scarf osteotomy significantly improved mid-term clinical outcomes.Ebina K., Hirao M., Tsuboi H., et al. Impact of combining medial capsule interposition with modified scarf osteotomy for hallux valgus. Modern Rheumatology 30, 204 (2020); https://doi.org/10.1080/14397595.2019.1572261

Effects of follow-on therapy after denosumab discontinuation in patients with postmenopausal osteoporosis

Objectives: To clarify the effects of follow-on therapy after denosumab (DMAb) discontinuation. Methods: In this retrospective, multicenter study, postmenopausal patients with osteoporosis who were previously treated by oral bisphosphonates (BP) (n = 26) or teriparatide (TPTD) (n = 27) were switched to DMAb (administered 2.6 times), and then discontinued. Patients (73.1 years, T-scores of the lumbar spine [LS] − 2.7 and femoral neck [FN] − 2.2) were switched to either (1) raloxifene (RAL) (n = 13) or BP [(2) weekly or monthly BP (wmBP) (n = 29) or (3) zoledronate (ZOL) (n = 11)], based on each physician’s decision (mean interval after final DMAb administration was 7.2 months). Bone mineral density (BMD) at final DMAb administration were set as baseline. Results: Changes in LS BMD at 1.5 years after final DMAb administration were −2.7% in the RAL, 0.7% in the wmBP, and 1.9% in the ZOL (p =.31 between groups), and in FN BMD were −3.8%, −0.8%, and 1.8%, respectively (p =.02 between the RAL and ZOL; p =.048 between the RAL and BP). Clinical vertebral fracture incidence during 1.5 years after final DMAb administration was 23.1% in the RAL, 3.4% in the wmBP, and 0.0% in the ZOL (p =.048 between the RAL and ZOL; p =.015 between the RAL and BP). No significant differences were observed in these parameters between the wmBP and ZOL. Conclusion: These results may contribute to the selection of adequate follow-on therapy after DMAb discontinuation, although further investigations are required.Ebina K., Hashimoto J., Kashii M., et al. Effects of follow-on therapy after denosumab discontinuation in patients with postmenopausal osteoporosis. Modern Rheumatology 31, 485 (2021); https://doi.org/10.1080/14397595.2020.1769895