Investigating the Microchannel Architectures Inside the Subchondral Bone in Relation to Estimated Hip Reaction Forces on the Human Femoral Head

Abstract

The interplay between articular cartilage (AC) and subchondral bone (SB) plays a pivotal role in cartilage homeostasis and functionality. As direct connective pathways between the two are poorly understood, we examined the location-dependent characteristics of the 3D microchannel network within the SB that connects the basal cartilage layer to the bone marrow (i.e. cartilage-bone marrow microchannel connectors; CMMC). 43 measuring points were defined on five human cadaveric femoral heads with no signs of osteoarthritis (OA) (age ≤ 60), and cartilage-bone cylinders with diameters of 2.00 mm were extracted for high-resolution scanning (n = 215). The micro-CT data were categorized into three groups (load-bearing region: LBR, n = 60; non-load-bearing region: NLBR, n = 60; and the peripheral rim: PR, n = 95) based on a gait analysis estimation of the joint reaction force (young, healthy cohort with no signs of OA). At the AC-SB interface, the number of CMMC in the LBR was 1.8 times and 2.2 times higher compared to the NLBR, and the PR, respectively. On the other hand, the median Feret size of the CMMC were smallest in the LBR (55.2 µm) and increased in the NLBR (73.5 µm; p = 0.043) and the PR (89.1 µm; p = 0.043). AC thickness was positively associated with SB thickness (Pearson's r = 0.48; p < 1e-13), CMMC number. (r = 0.46; p < 1e-11), and circularity index (r = 0.61; p < 1e-38). In conclusion, our data suggest that regional differences in the microchannel architecture of SB might reflect regional differences in loading.

Extracellular Vesicles Allow Epigenetic Mechanotransduction between Chondrocytes and Osteoblasts

“…Similarly, Wang et al reported that EVs containing miR-221-3p might attenuate OA by enhancing proliferation and migration of cartilage chondrocytes, but the exact mechanism was not further explored [27]. Considering the substantial mechanical/biochemical crosstalk between articular cartilage and subchondral bone [21,23,24], here, we studied EVs as a possible means for cell-cell communication between these tissues. In this regard, miR-221-3p was particularly interesting due to its mechanosensitive nature [16].…”

“…Based on our results, we hypothesize that the bone formation capacity of osteoblasts is regulated by the signal of miR-221-3p, mediated by EVs derived from chondrocytes. In previous studies, our group has demonstrated the existence of microchannel structures at the interface of bone and cartilage, which can potentially be pathways for the transportation of EVs and chondrocyte-osteoblast communication [22,23].…”

“…Due to its biomechanical properties, at the same load, cartilage is much more deformed than bone [18], making mechano-modulation of chondrocytes (e.g., via autocrine and paracrine signaling) a probable mechanism for the maintenance of joint homeostasis [19]. As in the joint, the subchondral bone is in direct contact with cartilage, and microchannels between the tissues theoretically allow cartilage-bone crosstalk [20][21][22][23][24]. The question remains if EVs can also modulate cells of the adjacent tissue, thereby translating the mechanical information into a tissue-bordertranscending epigenetic signal.…”

The Interaction between microRNAs and the Wnt/β-Catenin Signaling Pathway in Osteoarthritis

“…EVs have been shown to mediate cell-cell communication by transferring cargos containing miRNAs, and the bilayer of EVs can protect miRNAs from RNase-induced degradation during the transportation process. Given the existence of microchannels between cartilage and bone [100,101], EVs mediated miRNAs' regulation on Wnt signaling could be a center of attraction for innovation and an important area to perform an in-depth study of cell-cell communication between the joint tissues.…”

The Application of Extracellular Vesicles Mediated miRNAs in Osteoarthritis: Current Knowledge and Perspective

“… 15 As nano-size membrane vesicles, EVs can be delivered quickly among tissues, even cross the microcrack channels and vessel channels between bone and cartilage interface, facilitating bone-cartilage communication. 16 More importantly, the lipid bilayer of EVs could protect the miRNAs from degradation during the transportation process. 17 With the intercellular communication capability, EVs have been exploited to deliver exogenous therapeutic reagents for decades.…”