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Uniaxially fixed mechanical boundary condition elicits cellular alignment in collagen matrix with induction of osteogenesis.

ABSTRACT: Osteocytes differentiated from osteoblasts play significant roles as mechanosensors in modulating the bone remodeling process. While the well-aligned osteocyte network along the trabeculae with slender cell processes perpendicular to the trabeculae surface is known to facilitate the sensing of mechanical stimuli by cells and the intracellular communication in the bone matrix, the mechanisms underlying osteocyte network formation remains unclear. Here, we developed a novel in vitro collagen matrix system exerting a uniaxially-fixed mechanical boundary condition on which mouse osteoblast-like MC3T3-E1 cells were subcultured, evoking cellular alignment along the uniaxial boundary condition. Using a myosin II inhibitor, blebbistatin, we showed that the intracellular tension via contraction of actin fibers contributed to the cellular alignment under the influence of isometric matrix condition along the uniaxially-fixed mechanical boundary condition. Furthermore, the cells actively migrated inside the collagen matrix and promoted the expression of osteoblast and osteocyte genes with their orientations aligned along the uniaxially-fixed boundary condition. Collectively, our results suggest that the intracellular tension of osteoblasts under a uniaxially-fixed mechanical boundary condition is one of the factors that determines the osteocyte alignment inside the bone matrix.

SUBMITTER: Kim J

PROVIDER: S-EPMC8079399 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:IntroductionAlignment goals in total knee replacement (TKR) is a topical subject. This study compares the short-term functional outcomes and patient reported outcome measures (PROMs) of two philosophies for knee arthroplasty alignment: measured resection (MR) and an individualised alignment philosophy, with the tibia mechanically aligned and an instrumented gap balancer (GB) to align the femur in both flexion and extension.Patients and methods94 knees were enrolled in this randomised controlled trial. The surgical protocol used a MR technique for mechanical alignment or a GB technique for individualised alignment. Primary outcome was quadriceps strength. Secondary outcomes included validated functional tests and PROMs as well as patient satisfaction. Outcomes were assessed pre-operatively, at 6 weeks, 3, 6 and 12 months post-operatively.ResultsAt 12-month follow-up, there was no significant difference in the change from baseline mean quadriceps peak torque between the two groups (p = 0.988). Significant improvement in the change in range of motion (ROM) in the GB group compared to the MR group at 3 months (13° vs 6° p = 0.028) but this improvement was not significant at 1 year (20° vs 17° p = 0.21). The functional test of balance showed statistically significant improvement at 6 weeks (p = 0.03) in the GB group but this difference was not maintained. PROMs favoured the GB group, with the KOOS pain scoring statistically better (p ≤ 0.05) at 6 weeks, 3, 6 and 12 months.ConclusionsIndividualised alignment philosophy utilising a GB technique did not demonstrate an improvement in the primary outcome measure quadriceps peak torque. Improvement was seen in the GB group in PROM pain scores that was significant, both statistically and clinically, out to at least 1 year. Gains that were seen in functional assessment with GB, although significant at some time points, were no longer significant at 1 year and no difference was seen in quads strength. Compared to a MR technique, the individualised GB technique appears to confer some improvement in pain, ROM and some functional tests following TKR in the short-term.

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Uniaxially fixed mechanical boundary condition elicits cellular alignment in collagen matrix with induction of osteogenesis.

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