Obesity and load-induced posttraumatic osteoarthritis in the absence of fracture or surgical trauma.

Osteoarthritis is increasingly viewed as a heterogeneous disease with multiple phenotypic subgroups. Obesity enhances joint degeneration in mouse models of posttraumatic osteoarthritis (PTOA). Most models of PTOA involve damage to surrounding tissues caused by surgery/fracture; it is unclear if obesity enhances cartilage degeneration in the absence of surgery/fracture. We used a nonsurgical animal model of load-induced PTOA to determine the effect of obesity on cartilage degeneration 2 weeks after loading. Cartilage degeneration was caused by a single bout of cyclic tibial loading at either a high or moderate load magnitude in adult male mice with severe obesity (C57Bl6/J + high-fat diet), mild obesity (toll-like receptor 5 deficient mouse [TLR5KO]), or normal adiposity (C57Bl6/J mice + normal diet and TLR5KO mice in which obesity was prevented by manipulation of the gut microbiome). Two weeks after loading, cartilage degeneration occurred in limbs loaded at a high magnitude, as determined by OARSI scores (P < .001). However, the severity of cartilage damage did not differ among groups. Osteophyte width and synovitis of loaded limbs did not differ among groups. Furthermore, obesity did not enhance cartilage damage in limbs evaluated 6 weeks after loading. Constituents of the gut microbiota differed among groups. Our findings suggest that, in the absence of surgery/fracture, obesity may not influence cartilage loss after a single mechanical insult, suggesting that either damage to surrounding tissues or repeated mechanical insult is necessary for obesity to influence cartilage degeneration. These findings further illustrate heterogeneity in PTOA phenotypes and complex interactions between mechanical/metabolic factors in cartilage loss.

Mechanically induced bone formation is not sensitive to local osteocyte density in rat vertebral cancellous bone.

Osteocytes play an integral role in bone by sensing mechanical stimuli and releasing signaling factors that direct bone formation. The importance of osteocytes in mechanotransduction suggests that regions of bone tissue with greater osteocyte populations are more responsive to mechanical stimuli. To determine the effects of osteocyte population on bone functional adaptation we applied mechanical loads to the 8th caudal vertebra of skeletally mature female Sprague Dawley rats (6 months of age, n = 8 loaded, n = 8 sham controls). The distribution of tissue stress/strain within cancellous bone was determined using high-resolution finite element models, osteocyte distribution was determined using nano-computed tomography, and locations of bone formation were determined using three-dimensional images of fluorescent bone formation markers. Loading increased bone formation (3D MS/BS 10.82 ± 2.09% in loaded v. 3.17 ± 2.05% in sham control, mean ± SD). Bone formation occurred at regions of cancellous bone experiencing greater tissue stress/strain, however stress/strain was only a modest predictor of bone formation; even at locations of greatest stress/strain the probability of observing bone formation did not exceed 41%. The local osteocyte population was not correlated with locations of new bone formation. The findings support the idea that local tissue stress/strain influence the locations of bone formation in cancellous bone, but suggest that the size of the osteocyte population itself is not influential. We conclude that other aspects of osteocytes such as osteocyte connectivity, lacunocanilicular nano-geometry, and/or fluid pressure/shear distributions within the marrow space may be more influential in regulating bone mechanotransduction than the number of osteocytes. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:672-681, 2018.