Page 77 - OR-1-3

Peroxidase, secreted by eosinophils, inhibits osteoclast the premature termination of the patient’s height growth
overactivation and plays a protective homeostatic role and the development of short stature. This pathological
249
in inflammation. Macrophages, as osteoclast precursors process fully reflects the importance of precise regulation
and microenvironmental coordinators, dominate bone of hormone levels, which is achieved through the positive
homeostasis, injury repair, and pathological destruction by and negative feedback regulation of the endocrine
secreting signaling molecules and intercellular contacts. 246 system. Feedback regulatory mechanisms ensure that
hormone levels are maintained within a narrow range of
From this perspective, the immune system plays an
indispensable role in the development and normal function physiological requirements and that they respond precisely
and dynamically to adaptive changes in the external and
of MSK organoids. The absence of the immune system may internal environment. The absence of this mechanism is
lead to an imbalance in the osteoblast-osteoclast coupling particularly evident in the field of organoid research. For
due to the lack of T-cell-derived RANKL. It may also example, corticosteroids are unable to mimic clinically
245
result in the sustained release of local inflammatory signals important phenomena, such as adrenal suppression and
from injured tissues due to the absence of neutrophils and disturbances in endogenous cortisol secretion resulting
macrophages, leading to delayed regeneration. The absence from long-term drug use in organoid models that lack
of an immune microenvironment significantly hinders negative feedback regulation. This lack may lead to grossly
progress in MSK organoid research. To establish an effective underestimating the risk of drug-induced rhabdomyolysis
immune microenvironment in MSK organoids, co-culture or ignoring the adverse effects, such as muscle weakness,
247
is a mature and feasible method. Researchers can simulate that may occur after drug withdrawal. 250,251 Of greater
the immune microenvironment in the MSK system by concern is the fact that organoids are cultured in isolation
combining cells, drugs, or gene editing technologies. In so that they can neither sense and respond to changes in
addition, the development of microfluidic chip technology the whole-body state nor trigger the complete endocrine
enables researchers to precisely regulate cell interactions cascade. This endocrine dysfunction impairs hormonal
and the delivery of soluble factors in co-culture systems. regulation of organoids, a process often critical in clinical
These methods provide powerful tools for studying the applications, thereby compromising the functionality
dynamic interactions between immune cells and MSK of MSK organoid models. These limitations suggest that
organoids, accurately simulating key pathological processes the development of organoid technology should focus
such as RA, OP, and muscle atrophy. on constructing culture systems that closely resemble

5.1.4. Absence of hormonal regulation the in vivo microenvironment and integrating dynamic
hormone regulatory networks to more accurately mimic
The endocrine system realizes the precise regulation of the complex physiological and pathological processes in
the MSK system at multiple levels through hormonal the human body.
messengers, and its mechanism of action is both extensive
and complex. During the development of the MSK system, 5.1.5. Difficult to reproduce mechanical stimuli
the growth hormone/IGF axis and the hypothalamus- As the core system responsible for human limb movement,
248
pituitary-thyroid axis play a critical regulatory role. the development, maintenance, and functional realization
Activation of these endocrine axes is capable of finely of the MSK system are always closely linked to mechanical
regulating bone and muscle growth processes. However, stimulus signals. In a complex biomechanical
252
hormone release is not simply constant, but shows a highly environment, the bone is continuously subjected to
dynamic pattern that includes pulsatile secretion, circadian a variety of stresses, such as compression, bending,
fluctuations, and stress-responsive release. This complex and torsion. Moreover, its density and microstructure
pattern of secretion enables the endocrine system to be are dynamically remodeled in response to changes in
precisely regulated according to the needs of the organism, mechanical loading. Muscle fibers are subjected to active
but, at the same time, poses a great challenge for in vitro contraction and passive pulling forces, adjusting their
studies. Although significant progress has been made in thickness in response to changes in strength training.
organoid culture technology, it is still unable to realistically Joints are subjected to repeated cyclic compressive and
simulate the dynamic hormone fluctuation environment shear stresses to maintain interface lubrication and limb
in the human body, which is a limitation that may lead to mobility. These phenomena profoundly reveal the high
serious bias in drug screening and organ function studies. dependence and active adaptation of the MSK system
In the case of juvenile thyrotoxicosis, for example, the to mechanical stimuli. From the cellular and molecular
disease is caused by abnormally high levels of thyroid level, mechanical signaling is a key regulator that is
hormone release. Excessive thyroid hormone accelerates indispensable for maintaining the maturation phenotype
the process of bone development, leading to premature of cells, such as osteoblasts, chondrocytes, and tendon
fusion of the growth plates, which ultimately results in cells. In the absence of appropriate mechanical stimulation,

Volume 1 Issue 3 (2025) 19 doi: 10.36922/OR025280024