Biology subjects

Tjandra, P. M.

Publications and source records attributed to Tjandra, P. M..

2 recordsLinked to original sources

bioRxiv2025

Complement factor D (adipsin) mediates pressure-pain hypersensitivity post destabilization of medial meniscus injury

BACKGROUNDAlthough osteoarthritis (OA) is the leading cause of pain and disability worldwide, there is a lack of models to probe the separable mechanism of OA structural damage and knee pain. We previously identified that deletion of complement factor D (FD) results in increased pressure-pain hyperalgesia despite cartilage protection after destabilization of the medial meniscus (DMM) surgery. However, how these discordant OA phenotypes manifest is not understood. We employed a novel targeted lipidomics approach to elucidate the role of eicosanoids in FD-mediated pain. We hypothesize that the absence of Cfd (FD-/-) will protect cartilage but cause increased pressure-pain hyperalgesia and eicosanoid dysregulation that persists throughout OA development. METHODSMale and female FD-/- and wild-type (WT) mice were challenged with DMM or remained naive (n=5-11/group) at 16 weeks old. Pressure-pain hyperalgesia was measured bi-weekly for 8 weeks post-DMM. A second cohort was evaluated at 2 weeks post-DMM (n=6-10/group) to investigate DMM injury response. Structural damage was scored using the Modified Mankin system. To determine changes in eicosanoid profiles, serum and synovial fluid samples were analyzed via liquid chromatography-mass spectrometry (LC-MS). Statistical analysis was performed with unpaired t-test, two-way, or three-way ANOVA with Sidaks posthoc test. Statistical significance is defined as p<0.05. RESULTSIn contrast to WT mice, FD-/- showed no significant differences in Modified Mankin scores 8 weeks post-DMM. As expected, FD-/- hyperalgesia levels persisted until 8 weeks post DMM, similar to WT. Changes in eicosanoid profiles of pain-associated factors in FD-/-when compared to WT were found in the synovial fluid at 2 weeks and the serum at 8 weeks post-DMM. CONCLUSIONThe absence of Cfd drives knee hyperalgesia in male and female mice at 2 weeks-post DMM and persists through an 8-week observation period despite observing cartilage protection. Changes of eicosanoid profiles at both time points suggest that FD drives pain acutely, and the hyperalgesia phenotype emerges early in response to DMM injury, elucidating the role of the alternative complement in mediating OA pain and structural damage.

physiology↗

bioRxiv2020

Systemic Bone Loss Following Myocardial Infarction in Mice is Mitigated by Treatment with a β3 Adrenergic Receptor Antagonist

Myocardial infarction (MI) and osteoporotic fracture (Fx) are leading causes of morbidity and mortality worldwide, and there is epidemiological evidence linking their incidence, suggesting possible crosstalk. MI can exacerbate underlying atherosclerosis through sympathetic nervous system activation and {beta}3 adrenoreceptor-mediated release of hematopoietic stem cells (HSCs), leading to monocytosis. We hypothesized that this same pathway may initiate systemic bone loss following MI, since osteoclasts differentiate from monocytes. In this study, MI was performed in 12-week-old male mice (n=24), and mice were randomized to treatment with a {beta}3-adrenergic receptor antagonist (SR 59230A) or no treatment for 10 days post-operatively; additional mice (n=21, treated and untreated) served as un-operated controls. Bone mineral density (BMD), bone mineral content (BMC), and body composition were quantified at baseline and 10 days post-MI using DXA; at 10 days post-MI circulating monocyte and neutrophil levels were quantified, and the L5 vertebral body and femur were analyzed with micro-computed tomography. We found that MI led to increases in circulating monocyte and neutrophil levels, but contrary to our initial hypothesis, {beta}3-antagonist treatment further increased circulating monocytes compared to untreated mice. BMD and BMC of MI mice decreased at the femur and lumbar spine (-6.9% femur BMD, -3.5% lumbar BMD); {beta}3-antagonist treatment diminished this bone loss response (-5.3% femur BMD, -1.2% lumbar BMD). Similarly, trabecular bone volume was decreased in MI mice compared to control mice, and this bone loss was partially attenuated by {beta}3-antagonist treatment. These results suggest that MI leads to bone loss at both the axial and appendicular skeleton, and that the sympathetic nervous system may be a modulator of this response. This study is the first to mechanistically show bone loss following an ischemic injury; these findings suggest that bone loss and increased fracture risk may be important clinical co-morbidities following MI or other ischemic injuries.

physiology↗